Abstract—
Aim: The aim of the present work was to evaluate associations between the risk of endometriosis and -460C/T (rs833061) and +405G/C (rs2010963) polymorphisms in the VEGF gene.
Methodology: In the present study, we examined group of 100 patients with endometriosis and 100 controls. Genomic DNA was extracted from peripheral blood. Determination of genes polymorphic variants was made using polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP).
Results: Presented study showed statistically significant increase in the endometriosis development risk for the -460T/T genotype (OR 3.39; 95% CI, 1.60-7.13; p = 0.002) and for the -460T allele (OR 2.49; 95% CI, 1.64-3.78; p <.0001), as well as for the +405C/C genotype (OR 2.16; 95% CI, 1.047-4.48; p = 0.035) in patients with endometriosis in comparison with healthy control group. We also observed positive association of the +405C/C genotype (OR 0.26; 95% CI, 0.08-0.79; p = 0.019) as well as the +405C allele occurrence with an increased endometriosis development risk (OR 0.31; 95% CI, 0.19-0.71; p = 0.005), assessed by the degree of rASRM classification stages.
Conclusion: The results support the hypothesis that the -460C/T and +405G/C polymorphisms of the VEGF gene may be associated with endometriosis occurrence in Poland.
Keywords— endometriosis, genetic polymorphisms, VEGF.
Ebmt 2018 gps in mm koehne et al_with suppl slides_final_final_1.1.12_mar2018...Nicholas Sarlis
Galinpepimut-S (WT1-targeting peptide vaccine) in high-risk multiple myeloma. Final results from a Phase 2 clinical study. Koehne G, et al. EBMT 2018 slide presentation.
Interleukin16 and Interleukin 28B Genes Polymorphism in HBV Infected Saudi pa...iosrjce
The course of hepatitis B virus (HBV) infection is variable depending on many factors. In this study,
we investigated single nucleotide polymorphisms of interleukin-28B and interleukin-16 as possible host factors
which may determine the occurrence of hepatocellular carcinoma (HCC) in Saudi patients. Chronic hepatitis B
(CHB) patients (75), HCC patients (42), and healthy controls (70) were analyzed for polymorphisms of the IL16
and IL28B genes using PCR and restriction fragment length polymorphism (RFLP). Results showed that HCC
and chronic HBV patients had higher prevalence of rs11556218TG genotype than controls. The rs11556218GG
genotype was higher among HCC (14.4%) compared to chronic HBV (2.7%) patients. The IL-16 genotype
rs4072111CT was higher among HCC (47.6%) and chronic HBV (46.7%) patients than controls (28.6%). The
rs4072111TT genotype was higher among HCC patients compared to the other two groups. The T allele
frequency was higher among HCC patients than controls. The CT and TT of the IL-28B rs12979860 genotype
were significantly less frequent in chronic HBV and HCC patients. The IL-28B rs8099917 TG genotype was
more frequent among HCC (19%) compared to chronic HBV (8%) patients. However, no significant difference
was detected in the allele distribution.
Geriatric Care at a Time of Accelerated Aging in the World Population and Eme...science journals
It is a well-known fact that the world population has been aging since mid-20th century. The number of older people aged 60 years and above has more than quadrupled since 1950’s and older people’s share of the world population reached 11.7 percent in 2013.
OSU-03012 sensitizes breast cancers to lapatinib-induced cell killing: a role...Enrique Moreno Gonzalez
Lapatinib is characterized as an ErbB1/ErbB2 dual inhibitor and has recently been approved for the treatment of metastatic breast cancer. In this study, we examined mechanisms
associated with enhancing the activity of lapatinib via combination with other therapies.
Ebmt 2018 gps in mm koehne et al_with suppl slides_final_final_1.1.12_mar2018...Nicholas Sarlis
Galinpepimut-S (WT1-targeting peptide vaccine) in high-risk multiple myeloma. Final results from a Phase 2 clinical study. Koehne G, et al. EBMT 2018 slide presentation.
Interleukin16 and Interleukin 28B Genes Polymorphism in HBV Infected Saudi pa...iosrjce
The course of hepatitis B virus (HBV) infection is variable depending on many factors. In this study,
we investigated single nucleotide polymorphisms of interleukin-28B and interleukin-16 as possible host factors
which may determine the occurrence of hepatocellular carcinoma (HCC) in Saudi patients. Chronic hepatitis B
(CHB) patients (75), HCC patients (42), and healthy controls (70) were analyzed for polymorphisms of the IL16
and IL28B genes using PCR and restriction fragment length polymorphism (RFLP). Results showed that HCC
and chronic HBV patients had higher prevalence of rs11556218TG genotype than controls. The rs11556218GG
genotype was higher among HCC (14.4%) compared to chronic HBV (2.7%) patients. The IL-16 genotype
rs4072111CT was higher among HCC (47.6%) and chronic HBV (46.7%) patients than controls (28.6%). The
rs4072111TT genotype was higher among HCC patients compared to the other two groups. The T allele
frequency was higher among HCC patients than controls. The CT and TT of the IL-28B rs12979860 genotype
were significantly less frequent in chronic HBV and HCC patients. The IL-28B rs8099917 TG genotype was
more frequent among HCC (19%) compared to chronic HBV (8%) patients. However, no significant difference
was detected in the allele distribution.
Geriatric Care at a Time of Accelerated Aging in the World Population and Eme...science journals
It is a well-known fact that the world population has been aging since mid-20th century. The number of older people aged 60 years and above has more than quadrupled since 1950’s and older people’s share of the world population reached 11.7 percent in 2013.
OSU-03012 sensitizes breast cancers to lapatinib-induced cell killing: a role...Enrique Moreno Gonzalez
Lapatinib is characterized as an ErbB1/ErbB2 dual inhibitor and has recently been approved for the treatment of metastatic breast cancer. In this study, we examined mechanisms
associated with enhancing the activity of lapatinib via combination with other therapies.
Single Nucleotide Polymorphism Genotyping Using Kompetitive Allele Specific ...MANGLAM ARYA
Single Nucleotide Polymorphism
Single nucleotide polymorphism (SNP) refers to a single base change in a DNA sequence
SNP: Commonly biallelic
Two types(Based on presence in genome)
Synonymus
Non-synonymus
SNPs have largely replaced simple sequence repeats (SSRs)
Advantage of using SNPs
Low assay cost
High genomic abundance
Locus specificity
co-dominant inheritance
Simple documentation
Potential for high-throughput Analysis
Relatively low genotyping error rates
SNP genotyping platforms
BeadXpressTM,GoldenGateTM and Infinium from Illumina
GeneChipTM and GenFlexTM Tag array from Affimetrix
SNaPshotTM and TaqManTM from the Applied Biosystems
SNPWaveTM from KeyGene
iPLEX GoldTM Assay and Mass-RRAYTM from Sequonome
Variables to be considered
Throughput
Data turnaround
Time
Ease of use
Performance (sensitivity, reliability, reproducibility, and accuracy),
Flexibility (genotyping few samples with many snps or many samples with few snps),
Number of markers generated per run (uniplex versus multiplex assay capability)
Assay development requirements and genotyping cost per sample or data point.
KASP
KBioscience Competitive Allele-Specific PCR
Homogenous, Fluorescence-based genotyping technology, based on
Allele-specific oligo extension (primer)
Fluorescence resonance energy transfer
KASP Applications
Genotyping a wide range of species for various purposes.
KASP for Quality analysis, QTL mapping, MARS, and allele mining
Quality Control Analysis
QC analysis should be done for two reasons by genotyping the parents and F1s with the same subset of SNPs, in order to
confirm if F1s contains true-to-type alleles from their parents
check the genetic purity of the inbred parents.
F1s with true-to-type parental alleles for at least 90 % of the SNPs that were polymorphic between the parents should be advanced, while those with less than 10 % nonparental alleles should be discarded.
QTL Mapping
QTL mapping identifies a subset of markers that are significantly associated with one or more QTL influencing the expression of the trait of interest.
1) Select or develop a bi-parental mapping population.
2) Phenotype the population for a trait under greenhouse or field conditions.
3) Choose a molecular marking system – genotype parents of the mapping population and F1s with large numbers of markers, then select 200-400 markers exhibiting polymorphism between the parents.
4) Choose a genotyping approach, then generate molecular data for polymorphic markers
5) Identify the molecular markers associated with major QTL using statistical programs.
Large-scale allele mining
Allele mining is a promising approach to dissecting naturally occurring allelic variation at candidate genes controlling key agronomic traits.
KASP platform at CIMMYT has been used for the systematic mining of large germplasm collections for specific functional polymorphisms.
SNPs or small indels that
Single Nucleotide Polymorphism Analysis
Predictive Analytics and Data Science Conference May 27-28
Asst. Prof. Vitara Pungpapong, Ph.D.
Department of Statistics
Faculty of Commerce and Accountancy
Chulalongkorn University
general information regarding single nucleotide polymorphism.
A Single Nucleotide Polymorphisms (SNP), pronounced “snip,” is a genetic variation when a single nucleotide (i.e., A, T, C, or G) is altered and kept through heredity.
hMSH2 Gly322Asp (rs4987188) Single nucleotide polymorphism and the risk of br...Agriculture Journal IJOEAR
Aim: Breast cancer is the most common cancer in women both in the developed and less developed world. The reported study was designed to explore associations between hMSH2 - Gly322Asp (1032G>A, rs4987188) single nucleotide polymorphism (SNP) and the risk of breast carcinoma in the Polish women.
Material and methods: Blood samples were obtained from women with breast cancer (n=225), treated at the Department of Oncological Surgery and Breast Diseases, Polish Mother’s Memorial Hospital – Research Institute between the years 2005 and 2012. A control group included 220 cancer-free women. Genomic DNA was isolated and the SNP Gly322Asp of hMSH2 was determined by High-Resolution Melter method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each genotype and allele.
Results: This study revealed that single nucleotide polymorphism Gly322Asp of hMSH2 is associated with both breast cancer risk and grading. Moreover, it can be linked with breast carcinoma tumor size and lymph node status. The Asp allele in patients may be a risk factor for breast carcinoma (OR 5.12; 95% CI 3.77 –6.97, p<.0001).
Conclusions: Gly322Asp single nucleotide polymorphism of hMSH2 may be a risk factor of breast cancer in the Polish women.
Polymorphism in Glutatione S-Transferase P1 and ManganeseSuperoxide Dismmutas...iosrjce
Susceptibility to preeclampsia is believed to have a genetic component. Several studies have reported
associations between polymorphisms of oxidative stress- related genes and preeclampsia. The aim of the present
study was to study the polymorphisms in anti-oxidant genes glutathione S-transferase P1 (GSTP1) and Mnsuperoxide
dismutase (Mn-SOD) in patients with of preeclampsia. Seventy four preeclampsia patients and fifty
age-matched healthy pregnant female controls were genotyped for GSTP1 and Mn-SOD. DNA was extracted
from peripheral blood of all patients and control women. DNA analysis was carried out by polymerase chain
reaction (PCR), and then digestion of the PCR products by restriction enzymes (RFLP) for both genes was
performed. As regards GSTP1, the carriers of Val (G) allele were significantly more frequent among
preeclampsia patients when compared to the control group (45.95% Vs. 19%, X
2=10.40, OR=2.418, 95%CI
(1.3698 - 4.269); p=0.0023). Preeclampsia patients had a lower frequency of GSTP1 Ile/Ile (AA) genotype
(31.1% Vs. 68% in control; X
2=13.09, OR=0.457, 95%CI (0.241 - 0.866); p =0.0164). The frequency of
GSTP1 Ile/Val (AG) and Val/Val (GG) genotypes was higher in preeclampsia patients than control (68.9%Vs.
32%; X
2= 12.83, OR=2.154, 95%CI (1.106 - 4.194); p =0.0241). However, non significant frequencies
differences as regards Mn-SOD genotypes or alleles were found between preeclampsia patients and control. It
could be concluded that, pregnant Egyptian women carrying the Val (G) allele of GSTP1 GSTP1 -105 Ile →Val
(-313 A to G) polymorphism may be more susceptible to preeclampsia either in homozygous or heterozygous state
Association of common palb2 polymorphisms with ovarian cancer a case control ...IJARIIT
Background: The partner and localizer of breast cancer 2 (PALB2) has an essential role in BRCA2 mediated DNA
double-strand break repair by serving as a bridging molecule and acting as the physical and functional link between BRCA1&
2 proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risk of developing
breast and /or ovarian cancer in different populations. The present study was designed to investigate the variants of PALB2 and
their association with OC.
Material &Methods: A total of 150 histopathologically confirmed ovarian cancer patients and 250 healthy age matched controls
were collected. Three SNPs c.2794 G/A( rs45624036), c.1010 T/C(rs45494092), and c.1676A/G(rs152451) of PALB2 gene were
selected and genotyped by ARMS-PCR followed by agarose gel electrophoresis. Appropriate statistical tests were applied to test
for the significance of the results.
Results: A significant association of G/A (rs45624036) in inheritance models was observed & at the allelic level, the A allele
conferred four-fold increased risk compared to G allele. Regarding T/C (rs45494092) polymorphism all the models revealed an
association with OC and C allele showing eight-fold increased risk. With respect to A/G (rs152451) polymorphism, the protective
role was observed in tested inheritance models in OC patients.
The Haplo analysis for the combination of all the three variants revealed increased risk with A-T-A and G-C-G
haplotypes.(OR=4.50 ;95%CI 1.85-10.94;p=0.001,OR=26.36 ;95%CI 2.33 -297.91;p= 0.0085), whereas other haplotypes
conferred a protective role in OC.
Conclusions: The present study suggests an essential role of PALB2 in the etiology of ovarian cancer.
Background: Cervical screening through conventional cervical cytology is most commonly used throughout the world. The Cervical cancer is the second most common cancer worldwide and in developing countries, the leading cause of death. It is one of the most preventable and curable of all cancers.
Objective: To Study the role of Pap smear in detecting neoplastic and non-neoplastic lesions of cervix and to determine the occurrence of various lesions in remote area of Bagalkot.
Methods: This is prospective study of 240 women with age group 20 to 60 years was carried out from May 2015 to June 2016 cytology section of pathology department, S. Nijalingappa Medical College & H.S.K Hospital & Research Centre, Bagalkot, India. Pap smears were prepared, fixed, stained and carefully examined.
Results: In this study, Reactive cellular changes associated with inflammation was the most common with 182 cases (75.8%) followed by Low-grade squamous intraepithelial lesions (SIL) with 11 cases (4.5%), then atypical squamous epithelial cells of undetermined significance 8 cases (3.3%), High-grade squamous intraepithelial lesions with 5 cases (2.1%), Atrophy with 3 cases (1.3%) and Atypical Glandular Cell in 3 cases (1.3%). The average age of women for all the epithelial abnormalities was 40 years.
Conclusion: This study will increase awareness of the Pap test and cervical cancer, thereby paving a way for the prevention of cervical cancer.
Key-words- Pap smear, Cervical cancer, The Bethesda System, Squamous intraepithelial lesions (SIL)
Professor Michael Levin's presentation at Meningitis Research Foundation's 2013 conference Meningitis & Septicaemia in Children & Adults www.meningitis.org/conference2013
Robert P. Edwards, MD, Chair of OB/GYN/RS, Co-Director of Women's Cancer Program at University of Pittsburgh, offers information about the current state of immunotherapy for recurrent ovarian cancer patients.
Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell...semualkaira
anal squamous cell carcinoma (ASCC) is a relatively rare malignancy ac-counting for about 2-3% of all the gastrointestinal tumors. The standard of treatment for localized disease is chemoradiotherapy
Similar to The Single Nucleotide Polymorphisms (SNPS) of Vascular Endothelial Growth Factor (VEGF) Gene and Endometriosis (20)
WRI’s brand new “Food Service Playbook for Promoting Sustainable Food Choices” gives food service operators the very latest strategies for creating dining environments that empower consumers to choose sustainable, plant-rich dishes. This research builds off our first guide for food service, now with industry experience and insights from nearly 350 academic trials.
Characterization and the Kinetics of drying at the drying oven and with micro...Open Access Research Paper
The objective of this work is to contribute to valorization de Nephelium lappaceum by the characterization of kinetics of drying of seeds of Nephelium lappaceum. The seeds were dehydrated until a constant mass respectively in a drying oven and a microwawe oven. The temperatures and the powers of drying are respectively: 50, 60 and 70°C and 140, 280 and 420 W. The results show that the curves of drying of seeds of Nephelium lappaceum do not present a phase of constant kinetics. The coefficients of diffusion vary between 2.09.10-8 to 2.98. 10-8m-2/s in the interval of 50°C at 70°C and between 4.83×10-07 at 9.04×10-07 m-8/s for the powers going of 140 W with 420 W the relation between Arrhenius and a value of energy of activation of 16.49 kJ. mol-1 expressed the effect of the temperature on effective diffusivity.
Diabetes is a rapidly and serious health problem in Pakistan. This chronic condition is associated with serious long-term complications, including higher risk of heart disease and stroke. Aggressive treatment of hypertension and hyperlipideamia can result in a substantial reduction in cardiovascular events in patients with diabetes 1. Consequently pharmacist-led diabetes cardiovascular risk (DCVR) clinics have been established in both primary and secondary care sites in NHS Lothian during the past five years. An audit of the pharmaceutical care delivery at the clinics was conducted in order to evaluate practice and to standardize the pharmacists’ documentation of outcomes. Pharmaceutical care issues (PCI) and patient details were collected both prospectively and retrospectively from three DCVR clinics. The PCI`s were categorized according to a triangularised system consisting of multiple categories. These were ‘checks’, ‘changes’ (‘change in drug therapy process’ and ‘change in drug therapy’), ‘drug therapy problems’ and ‘quality assurance descriptors’ (‘timer perspective’ and ‘degree of change’). A verified medication assessment tool (MAT) for patients with chronic cardiovascular disease was applied to the patients from one of the clinics. The tool was used to quantify PCI`s and pharmacist actions that were centered on implementing or enforcing clinical guideline standards. A database was developed to be used as an assessment tool and to standardize the documentation of achievement of outcomes. Feedback on the audit of the pharmaceutical care delivery and the database was received from the DCVR clinic pharmacist at a focus group meeting.
Artificial Reefs by Kuddle Life Foundation - May 2024punit537210
Situated in Pondicherry, India, Kuddle Life Foundation is a charitable, non-profit and non-governmental organization (NGO) dedicated to improving the living standards of coastal communities and simultaneously placing a strong emphasis on the protection of marine ecosystems.
One of the key areas we work in is Artificial Reefs. This presentation captures our journey so far and our learnings. We hope you get as excited about marine conservation and artificial reefs as we are.
Please visit our website: https://kuddlelife.org
Our Instagram channel:
@kuddlelifefoundation
Our Linkedin Page:
https://www.linkedin.com/company/kuddlelifefoundation/
and write to us if you have any questions:
info@kuddlelife.org
Natural farming @ Dr. Siddhartha S. Jena.pptxsidjena70
A brief about organic farming/ Natural farming/ Zero budget natural farming/ Subash Palekar Natural farming which keeps us and environment safe and healthy. Next gen Agricultural practices of chemical free farming.
UNDERSTANDING WHAT GREEN WASHING IS!.pdfJulietMogola
Many companies today use green washing to lure the public into thinking they are conserving the environment but in real sense they are doing more harm. There have been such several cases from very big companies here in Kenya and also globally. This ranges from various sectors from manufacturing and goes to consumer products. Educating people on greenwashing will enable people to make better choices based on their analysis and not on what they see on marketing sites.
Micro RNA genes and their likely influence in rice (Oryza sativa L.) dynamic ...Open Access Research Paper
Micro RNAs (miRNAs) are small non-coding RNAs molecules having approximately 18-25 nucleotides, they are present in both plants and animals genomes. MiRNAs have diverse spatial expression patterns and regulate various developmental metabolisms, stress responses and other physiological processes. The dynamic gene expression playing major roles in phenotypic differences in organisms are believed to be controlled by miRNAs. Mutations in regions of regulatory factors, such as miRNA genes or transcription factors (TF) necessitated by dynamic environmental factors or pathogen infections, have tremendous effects on structure and expression of genes. The resultant novel gene products presents potential explanations for constant evolving desirable traits that have long been bred using conventional means, biotechnology or genetic engineering. Rice grain quality, yield, disease tolerance, climate-resilience and palatability properties are not exceptional to miRN Asmutations effects. There are new insights courtesy of high-throughput sequencing and improved proteomic techniques that organisms’ complexity and adaptations are highly contributed by miRNAs containing regulatory networks. This article aims to expound on how rice miRNAs could be driving evolution of traits and highlight the latest miRNA research progress. Moreover, the review accentuates miRNAs grey areas to be addressed and gives recommendations for further studies.
"Understanding the Carbon Cycle: Processes, Human Impacts, and Strategies for...MMariSelvam4
The carbon cycle is a critical component of Earth's environmental system, governing the movement and transformation of carbon through various reservoirs, including the atmosphere, oceans, soil, and living organisms. This complex cycle involves several key processes such as photosynthesis, respiration, decomposition, and carbon sequestration, each contributing to the regulation of carbon levels on the planet.
Human activities, particularly fossil fuel combustion and deforestation, have significantly altered the natural carbon cycle, leading to increased atmospheric carbon dioxide concentrations and driving climate change. Understanding the intricacies of the carbon cycle is essential for assessing the impacts of these changes and developing effective mitigation strategies.
By studying the carbon cycle, scientists can identify carbon sources and sinks, measure carbon fluxes, and predict future trends. This knowledge is crucial for crafting policies aimed at reducing carbon emissions, enhancing carbon storage, and promoting sustainable practices. The carbon cycle's interplay with climate systems, ecosystems, and human activities underscores its importance in maintaining a stable and healthy planet.
In-depth exploration of the carbon cycle reveals the delicate balance required to sustain life and the urgent need to address anthropogenic influences. Through research, education, and policy, we can work towards restoring equilibrium in the carbon cycle and ensuring a sustainable future for generations to come.
Willie Nelson Net Worth: A Journey Through Music, Movies, and Business Venturesgreendigital
Willie Nelson is a name that resonates within the world of music and entertainment. Known for his unique voice, and masterful guitar skills. and an extraordinary career spanning several decades. Nelson has become a legend in the country music scene. But, his influence extends far beyond the realm of music. with ventures in acting, writing, activism, and business. This comprehensive article delves into Willie Nelson net worth. exploring the various facets of his career that have contributed to his large fortune.
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Introduction
Willie Nelson net worth is a testament to his enduring influence and success in many fields. Born on April 29, 1933, in Abbott, Texas. Nelson's journey from a humble beginning to becoming one of the most iconic figures in American music is nothing short of inspirational. His net worth, which estimated to be around $25 million as of 2024. reflects a career that is as diverse as it is prolific.
Early Life and Musical Beginnings
Humble Origins
Willie Hugh Nelson was born during the Great Depression. a time of significant economic hardship in the United States. Raised by his grandparents. Nelson found solace and inspiration in music from an early age. His grandmother taught him to play the guitar. setting the stage for what would become an illustrious career.
First Steps in Music
Nelson's initial foray into the music industry was fraught with challenges. He moved to Nashville, Tennessee, to pursue his dreams, but success did not come . Working as a songwriter, Nelson penned hits for other artists. which helped him gain a foothold in the competitive music scene. His songwriting skills contributed to his early earnings. laying the foundation for his net worth.
Rise to Stardom
Breakthrough Albums
The 1970s marked a turning point in Willie Nelson's career. His albums "Shotgun Willie" (1973), "Red Headed Stranger" (1975). and "Stardust" (1978) received critical acclaim and commercial success. These albums not only solidified his position in the country music genre. but also introduced his music to a broader audience. The success of these albums played a crucial role in boosting Willie Nelson net worth.
Iconic Songs
Willie Nelson net worth is also attributed to his extensive catalog of hit songs. Tracks like "Blue Eyes Crying in the Rain," "On the Road Again," and "Always on My Mind" have become timeless classics. These songs have not only earned Nelson large royalties but have also ensured his continued relevance in the music industry.
Acting and Film Career
Hollywood Ventures
In addition to his music career, Willie Nelson has also made a mark in Hollywood. His distinctive personality and on-screen presence have landed him roles in several films and television shows. Notable appearances include roles in "The Electric Horseman" (1979), "Honeysuckle Rose" (1980), and "Barbarosa" (1982). These acting gigs have added a significant amount to Willie Nelson net worth.
Television Appearances
Nelson's char
The Single Nucleotide Polymorphisms (SNPS) of Vascular Endothelial Growth Factor (VEGF) Gene and Endometriosis
1. International Journal of Environmental & Agriculture Research (IJOEAR) ISSN:[2454-1850] [Vol-2, Issue-7, July- 2016]
Page | 163
The Single Nucleotide Polymorphisms (SNPS) of Vascular
Endothelial Growth Factor (VEGF) Gene and Endometriosis
Bożena Góralczyk1
, Krzysztof Szyłło2
, Hanna Romanowicz3
, Beata Smolarz4
1
Regional Hospital, 95-015 Glowno, Poland
E-mail bogora@mp.pl
2
Department of Surgical Gynaecology, Institute of Polish Mother’s Memorial Hospital, Rzgowska 281/289, 93-338 Lodz,
Poland
E-mail kszyllo@o2.pl
3
Laboratory of Cancer Genetics, Department of Pathology, Institute of Polish Mother’s Memorial Hospital, Rzgowska
281/289, 93-338 Lodz, Poland
E-mail hanna-romanowicz@wp.pl
4
Laboratory of Cancer Genetics, Department of Pathology, Institute of Polish Mother’s Memorial Hospital, Rzgowska
281/289, 93-338 Lodz, Poland
E-mail smolbea@wp.pl
Abstract—
Aim: The aim of the present work was to evaluate associations between the risk of endometriosis and -460C/T (rs833061)
and +405G/C (rs2010963) polymorphisms in the VEGF gene.
Methodology: In the present study, we examined group of 100 patients with endometriosis and 100 controls. Genomic DNA
was extracted from peripheral blood. Determination of genes polymorphic variants was made using polymerase chain
reaction-restriction fragment length polymorphism technique (PCR-RFLP).
Results: Presented study showed statistically significant increase in the endometriosis development risk for the -460T/T
genotype (OR 3.39; 95% CI, 1.60-7.13; p = 0.002) and for the -460T allele (OR 2.49; 95% CI, 1.64-3.78; p <.0001), as well
as for the +405C/C genotype (OR 2.16; 95% CI, 1.047-4.48; p = 0.035) in patients with endometriosis in comparison with
healthy control group. We also observed positive association of the +405C/C genotype (OR 0.26; 95% CI, 0.08-0.79; p =
0.019) as well as the +405C allele occurrence with an increased endometriosis development risk (OR 0.31; 95% CI, 0.19-
0.71; p = 0.005), assessed by the degree of rASRM classification stages.
Conclusion: The results support the hypothesis that the -460C/T and +405G/C polymorphisms of the VEGF gene may be
associated with endometriosis occurrence in Poland.
Keywords— endometriosis, genetic polymorphisms, VEGF.
I. INTRODUCTION
Endometriosis is a common gynaecological disease of unknown aetiology. Endometriosis is a multifactorial and polygenic
disease. Angiogenesis (the growth of blood vessels from pre-existing vasculature) is considered as a major process in the
pathogenesis of endometriosis. Many factors are involved in this complex mechanism such as cytokines (interleukins IL-1,
IL-6, IL-8, Tumor Necrosis Factor α (TNFα)), metalloproteinases (MMP1, MMP-3, MMP-9) and vascular endothelial
growth factors family (VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F) [1, 2].
VEGF is one of the most potent and specific angiogenic factors. VEGF is responsible for increased vascular permeability and
the proliferation of endothelial cells [3]. There are many causes indicating the role of vascular endothelial growth factor in
the development of endometriosis, such as expression of VEGF in stromal and epithelial cells and its regulation by estrogen
receptors α and β [4, 5].
Elevated concentrations of VEGF have been detected in the peritoneal fluid of patients with endometriosis [6-9].
VEGF gene has been mapped to chromosome 6p21.3 and is polymorphic in nature [10-12]. Polymorphisms within the 5′-
untranslated region (5-’UTR) lead to differences in VEGF expression level between individuals and could influence the
aetiology of a variety of pathological conditions with which VEGF has been associated. Several transcription factor-binding
sites are found in the VEGF 5′-UTR and variation within the region increases the transcriptional activity [13].
2. International Journal of Environmental & Agriculture Research (IJOEAR) ISSN:[2454-1850] [Vol-2, Issue-7, July- 2016]
Page | 164
Single nucleotide polymorphisms (SNPs) within the VEGF gene have been identified, some of which have functional
significance [14, 15]. Two common VEGF single nucleotide polymorphisms, +405G/C (rs2010963) and -460C/T (rs833061)
in the 5-′UTR have been reported to be associated with altered gene transcription [16, 17].
In the literature, many reports confirm the significance VEGF gene -460C/T and +405G/C polymorphism, regarding the risk
of endometriosis [18-29]. However, the reported results have rather been inconsistent [30, 31].
Little is known on the association between VEGF polymorphisms and endometriosis in Polish women. In the present work
we analysed an association between endometriosis and two single nucleotide polymorphisms occurring in VEGF gene: -
460C/T and +405G/C, respectively.
II. MATERIALS AND METHODS
1.1. Patients
In the present study, blood samples were obtained from 100 women with endometriosis, treated at the Department of
Gynaecology, Institute of Polish Mother's Memorial Hospital, Lodz, Poland between 2010-2012. The demographic data and
the pathologic features of the patients are summarized in Table 1. All the endometriosis samples were staged by a method,
based on the criteria of rASRM (The Revised American Society for Reproductive Medicine classification of endometriosis
1996). Blood samples from age- matched, endometriosis-free women (n = 100) served as control. The study was approved by
the Local Ethic Committee of the Institute of Polish Mother’s Memorial Hospital, Lodz, Poland and each patient gave a
written consent.
TABLE 1
THE CHARACTERISTIC OF ENDOMETRIOSIS PATIENTS* AND CONTROL GROUP*
Characteristic Patients N (%) Controls N (%)
Age
Mean ± SD
Range
Sex
Women
36.4 ± 6.0
23-58
100
38.3 ± 6.2
29-61
100
BMI (body mass index) (kg/m2
)
<25
25≤BMI<30
≥ 30
44 (44%)
48 (48%)
8 (8%)
42 (42%)
49 (49%)
9 (9%)
Number of birth
Yes
1
>2
No
46 (46%)
29 (29%)
17 (17%)
54 (54%)
49 (49%)
31 (31%)
18 (18%)
61 (61%)
Recurrent pregnancy loss
Yes
No
10 (10%)
90 (90%)
2 (2%)
98 (98%)
Use of hormone replacement therapy - HRT
Yes
No
46 (46%)
54 (54%)
21 (21%)
79 (79%)
rASRM classification
I
II
III
IV
11 (11%)
14 (14%)
44 (44%)
31 (31%)
*n=100
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Page | 165
1.2. DNA isolation
Genomic DNA was prepared using QIAmp Kit (Qiagen GmbH, Hilden, Germany) according to the manufacturer instruction.
1.3. Determination of VEGF -460C/T genotype
Polymorphism -460C/T of the VEGF gene was determined by PCR-RFLP, using primers: sense 5′-
TGTGCGTGTGGGGTTGAGCG-3′, antisense 5′- ACGTGCGGACAGGGCCTGA-3′ [15]. The PCR was carried out in a
PTC-100 TM (MJ Research, INC) thermal cycler. PCR amplification was performed in the final volume of 25 μl of reaction
mixture, which contained 100 ng of genomic DNA, 0.2 μmol of each primer (ARK Scientific GmbH Biosystems, Darmstad,
Germany), 2.5 mM of MgCl2, 1 mM of dNTPs and 1 unit of Taq Polymerase (Qiagen GmbH, Hilden, Germany). PCR cycle
conditions were the following: 94°C for 30s, 60°C for 30s and 72°C for 60s, repeated in 30 cycles. PCR products were
electrophoresed in a 2% agarose gel and visualised by ethidium bromide staining. The cleavage with BstU1 (New England
Biolabs), produced fragments of 175 and 20/155 bp corresponding to the T and C alleles of the VEGF gene, respectively.
The enzimatic digestion was controlled by negative controls. Negative controls contained dH2O (1 μl for 25 μl of PCR Mix).
1.4. Determination of +405 G/C genotype
Polymorphism +405G/C of the VEGF gene was determined by PCR-RFLP, using primers: sense 5′-
TTGCTTGCCATTCCCCACTTGA-3’, antisense 5′-CCGAAGCGAGAACAGCCCAGAA-3′ [32]. The PCR was carried out
in a PTC-100 TM (MJ Research, INC) thermal cycler. PCR amplification was performed in the final volume of 25 μl of
reaction mixture, which contained 100 ng of genomic DNA, 0.2 μmol of each primer (ARK Scientific GmbH Biosystems,
Darmstad, Germany), 2.5 mM of MgCl2, 1 mM of dNTPs and 1 unit of Taq Polymerase (Qiagen GmbH, Hilden, Germany).
PCR cycle conditions were the following: 94°C for 60s, 62°C for 30s and 72°C for 60s, repeated in 30 cycles. PCR products
were electrophoresed in a 2% agarose gel and visualised by ethidium bromide staining. The cleavage with BsmFI (New
England Biolabs), produced fragments of 469 and 196/273 bp corresponding to the C and G alleles of the VEGF gene,
respectively. The enzimatic digestion was controlled by negative controls. Negative controls contained dH2O (1 μl for 25 μl
of PCR Mix).
1.5. Statistical analysis
Logistic regression analysis was used to compute odds ratio (OR) and associated 95% confidence interval (95% CI) relating
each of the SNPs as well as combinations of SNPs and another analysed factors presented in Table 1 to the risk of
endometriosis. The observed numbers of each VEGF genotype were compared with those expected for a population in
Hardy-Weinberg equilibrium by using the Chi-square test. Genotype frequencies in the study cases and the controls were
compared by the Chi-square test. Wild type genotypes and alleles were used as reference groups. P-values < 0.05 were
considered significant. All the statistical analyses were performed, using the STATISTICA 6.0 software (Statsoft, Tulsa,
Oklahoma, USA).
III. RESULTS
Table 2 shows genotype distribution values of VEGF +405G/C polymorphisms in endometriosis patients and controls. An
association was found between the 405C/C genotype of the +405G/C polymorphism of VEGF gene and endometriosis
occurrence. In the examined patients, the observed frequencies of G/G, G/C and C/C genotypes differed significantly (p <
0.05) from the distribution range, as expected from the Hardy-Weinberg equilibrium.
TABLE 2
DISTRIBUTION OF GENOTYPES AND ALLELES FREQUENCY OF THE +405 G/C POLYMORPHISM OF THE VEGF
GENE IN PATIENTS WITH ENDOMETRIOSIS AND CONTROLS
Patients (N = 100)
N (%)
Controls (N = 100)
N (%) OR (95% CI)A
P
B
VEGF +405 G/C
G/G 24 (24) 26 (26) 1.00 Ref.
G/C 24 (24) 48 (48) 0.54 (0.25-1.13) 0.149
C/C 52 (52) 26 (26) 2.16 (1.04-4.48) 0.035
G 72 (36) 100 (50) 1.00 Ref.
C 128 (64) 100 (50) 0.90 (0.58-1.39) 0.729
Data in bold font are statistically significant
a
Crude odds ratio (OR), 95% CI = confidence interval at 95%, b
Chi square
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Table 3 shows genotype distribution of VEGF -460C/T polymorphism, illustrating the difference between the patients with
endometriosis and the controls. It can be seen from the Table 3 that there are significant differences in the frequency of
VEGF -460 C/T genotypes (p < 0.05) between the two investigated groups. A weak association was observed between
endometriosis occurrence and the presence of T/T genotypes. Variant 460T allele of VEGF increased endometriosis risk. In
case of the -460C/T polymorphism of VEGF gene the distribution of the genotypes in the patients differed significantly from
one expected from the Hardy-Weinberg equilibrium (p < 0.05).
TABLE 3
DISTRIBUTION OF GENOTYPES AND ALLELES FREQUENCY OF THE -460 C/T POLYMORPHISM OF THE VEGF
GENE IN PATIENTS WITH ENDOMETRIOSIS AND CONTROLS
Patients (N = 100)
N (%)
Controls (N = 100)
N (%) OR (95% CI)A
P
B
VEGF -460 C/T
C/C 16 (16) 28 (28) 1.00 Ref.
C/T 22 (22) 40 (40) 0.96 (0.43-2.15) 0.920
T/T 62 (62) 32 (32) 3.39 (1.60-7.13) 0.002
C 54 (27) 96 (48) 1.00 Ref.
T 146 (73) 104 (52) 2.49 (1.64-3.78) <.0001
Data in bold font are statistically significant
a
Crude odds ratio (OR), 95% CI = confidence interval at 95%, b
Chi square
We also analyzed combined genotype of all polymorphism pairs. Table 4 shows the haplotypes distribution of VEGF. The
haplotypes analysis according to wild-type of G405G–C460C showed high frequency C405C-T460T, genotype. The
combined C405C-T460T genotype increased the risk of endometriosis (OR=18, p=0.0001).
TABLE 4
HAPLOTYPES DISTRIBUTION AND FREQUENCIES OF VEGF GENE POLYMORPHISMS IN ENDOMETRIOSIS
PATIENTS AND THE CONTROLS
Haplotypes
VEGF-405-460
Patients
(N = 100)
N (%)
Controls
(N = 100)
N (%)
OR (95% CI)A
P
B
G/G-C/C 3 (3) 10 (10) 1.00 Ref.
G/C-C/C 5 (5) 12 (12) 1.38 (0.26-7.39) 0.514
C/C-C/C 8 (8) 3 (3) 8.88 (1.39-56.57) 0.043
G/G-C/T 3 (3) 8 (8) 1.25 (0.19-7.95) 0.589
G/C-C/T 3 (3) 16 (16) 0.62 (0.10-3.72) 0.469
C/C-C/T 14 (14) 13 (13) 3.58 (0.80-16.00) 0.082
C/C-T/T 27 (27) 5 (5) 18.00 (3.61-89.58) 0.0001
G/C-T/T 16 (16) 17 (17) 3.13 (0.72-13.05) 0.213
G/G-T/T 21 (21) 16 (16) 4.37 (1.03-18.55) 0.037
Data in bold font are statistically significant
NE - Not estimated.
a
Crude odds ratio (OR), 95% CI = confidence interval at 95%, b
Chi square
Endometriosis staging was related to VEGF polymorphisms. Endometriosis stage were evaluated in all the cases (n = 100).
Stages I+II and III+IV were accounted together for statistical analysis (see Table 5).
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TABLE 5
DEPENDENCE OF GENOTYPES AND FREQUENCIES OF VEGF GENE POLYMORPHISM ALLELES ON
ENDOMETRIOSIS STAGE IN PATIENTS
a
PATIENTS
stageb
I+II (n = 25) III+IV (n = 75) OR (95% CI)C
P
D
VEGF - 460C/T Number (%) Number (%)
C/C 4 (16) 15 (20) 1.00 Ref
C/T 8 (32) 17 (23) 1.76 (0.44-7.06) 0.639
T/T 13 (52) 43 (57) 1.13 (0.31-4.01) 0.560
C 16 (32) 47 (31) 1.00 Ref
T 34 (68) 103 (69) 0.96 (0.48-1.92) 0.920
VEGF +405G/C
G/G 9 (36) 13 (17) 1.00 Ref
G/C 8 (32) 17 (23) 0.68 (0.20-2.24) 0.740
C/C 8 (32) 45 (60) 0.26 (0.08-0.79) 0.019
G 26 (52) 43 (29) 1.00 Ref
C 24 (48) 107 (71) 0.31 (0.19-0.71) 0.005
Data in bold font are statistically significant
a
n = 100; b
according to rASRM classification; c
Crude odds ratio (OR), 95 % CI = confidence interval at 95 %, d
Chi square
No differences were observed in those groups, regarding either VEGF -460C/T genotype or allele distributions. Some
correlation was observed between the genotypes of VEGF +405G/C polymorphisms and endometriosis. A statistically
significant decrease was observed, regarding 405C allele frequency (OR 0.31; 95% CI 0.19 – 0.71, p = 0.005) in stage III+IV
patients, according to rASRM classification. A tendency for an increased risk of endometriosis was observed with the
occurrence of 405G allele of VEGF polymorphism.
No statistically significant differences were observed in the alleles or in the genotype frequencies of the VEGF gene
polymorphisms between risk factors of endometriosis such as BMI (body mass index), HRT (hormone replacement therapy)
and recurrent pregnancy loss and the women with endometriosis (data not shown).
IV. DISCUSSION
In the present study we genotyped two common polymorphisms of the VEGF gene and tested the association between the
distributions of their genotypes with endometriosis. The following SNPs were considered in the angiogenesis pathway:
VEGF -460C/T (rs833061) and +405G/C (rs2010963). The study was performed on an ethnically homogenous population,
which may improve our knowledge, regarding to what an extent the genotype-phenotype relationship variations are
population-related.
An important aspect of the association between endometriosis and VEGF, also for possible future therapeutic application is
that the single nucleotide polymorphisms in vascular endothelial growth factor gene are associated with the risk of
endometriosis.
VEGF gene consists of 8 exons. VEGF gene transcript undergoes alternative splicing processes to produce a protein family
[33]. There are a few transcription factor binding sites in 5’- UTR in VEGF gene [34]. From here, polymorphisms in this
region result in different levels of gene expression, causing various ranges of diseases such as endometriosis.
A G to C substitution at the position +405 and C to T substitution at the position -460 of the VEGF gene have been
describing as a single nucleotide polymorphisms. Both polymorphisms are located in the regulatory element (5'-untranslated
region) of the VEGF and are suggested to be associated with messenger RNA stability and expression [14, 15].
The –460C/T and +405G/C functional VEGF polymorphisms have been found to be associated with variation in VEGF
protein production [26, 15] and have been related to several diseases in which angiogenesis is involved [35-37].
6. International Journal of Environmental & Agriculture Research (IJOEAR) ISSN:[2454-1850] [Vol-2, Issue-7, July- 2016]
Page | 168
From a review of the literature we learned that VEGF –460C/T and +405G/C polymorphisms were investigated in diverse
populations with endometriosis. Many experimental studies confirm the significant role the influence of specific genetic
variants on endometriosis risk [18-20]. However the contribution of polymorphisms of VEGF gene in developing
endometriosis is controversial [29, 30].
This is the first study which attempted to analyse the incidence of alleles of the VEGF -460C/T and +405G/C
polymorphisms in samples from Polish women with endometriosis. In the presented study, VEGF +405C/C and -460T/T
genotype were associated with an elevated risk of endometriosis in the Polish population. There was an 18-fold increased risk
of endometriosis for C405C-T460T genotype carriers. Moreover +405G/C polymorphism was related to endometriosis stage.
We have also found that variant -460T allele of VEGF increased endometriosis risk. It is possible that the presence of the -
460T allele is in linkage disequilibrium with another, so far unknown, mutation located outside the coding region in the
VEGF gene, which may be of importance for the VEGF concentration in plasma and better endometriosis development.
Our results are in line with the data from other reports.
Analysis of the VEGF +405 G/C polymorphism in a Korean population showed that the single nucleotide polymorphism was
associated with the risk of advanced stage endometriosis [38].
The study of VEGF +405G/C in an Indian population identified a haplotype associated with endometriosis. Vanaja et al.
showed that the VEGF 405G/G genotype is associated with the risk of endometriosis in Indian women [18].
Emamifar et al. [19] found the correlation between the VEGF +405G/C polymorphism and endometriosis. The VEGF 405C
allele was associated with a significantly increased risk of endometriosis in northern Iran.
Similar results were obtained by Gentilini et al. in the Italian population [15]. Also, the analysis of Turkish women suggests
that VEGF gene polymorphisms in 5’-UTR are correlated wit endometriosis [20, 17].
However, other literature data were also found. No significant associations were observed between the VEGF -460C/T and
+405G/C polymorphism and endometriosis in Asians and Caucasians population [29, 30].
V. CONCLUSION
In conclusion, the presented study implies that -460C/T and +405G/C polymorphisms of the VEGF gene may be associated
with endometriosis in Polish women. The study was carried out on a relatively small patient population, thus the obtained
results cannot be considered as definitive and require further, more extensive evaluations, performed on bigger groups of
patients. However, our preliminary results are fairly promising, indicating a significant role of the polymorphisms of VEGF
genes for endometriosis development. It also appears from a thorough review of the medical literature that the
polymorphisms in VEGF gene, involved in the angiogenesis pathway, have for the first time been analyzed in endometriosis
patients in Poland. Thus we feel that our observations may be an important signal, prompting to appreciate the role of VEGF
in endometriosis occurrence and likely triggering further studies on this interesting subject.
ACKNOWLEDGEMENTS
This work was supported by grant N407098440 from the State of Scientific Research (KBN).
CONFLICTS OF INTEREST
The authors declare no conflicts of interest.
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