Vol 1,issue 7 Leptin receptor rs1137101 variant is risk factor for obesity and type II diabetes in Saudi adult women

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Genetic variations at the leptin receptor gene locus have been linked to diseases accompanying obesity and/or
obesity-related diseases in different populations.

However, the results from Previous studies have reported conflicting results. The aim of this study was to investigate whether LEPR gene SNP Gln223Arg (rs1137101) is associated with obesity and type II diabetes in Saudi adult women.

Therefore, SNP rs1137101 in LEPR gene in a total of 425 women (150 obese diabetic, 130 obese non-diabetic, and 145 normal weight) was investigated using PCR and sequencing techniques.

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Vol 1,issue 7 Leptin receptor rs1137101 variant is risk factor for obesity and type II diabetes in Saudi adult women

  1. 1. International Journal of Medical Sciences and Health Care Vol-1 Issue-7 (Ijmshc-703)
  2. 2. International Journal of Medical Sciences and Health Care Vol-1 Issue-7 (Ijmshc-703) http://www.ijmshc.com Page 14 Leptin receptor rs1137101 variant is risk factor for obesity and type II diabetes in Saudi adult women Rowyda .N. Al-Harithy, Noura .S. Al-Zahrani- Department of Biochemistry, King Abdulaziz University, Jeddah, Saudi Arabia. Address all correspondence to:Dr. Rowyda .N. Al-Harithy-Biochemistry Department,King Abdul Aziz University P. O. Box 40288 Jeddah 21499,Kingdom of Saudi Arabia. Abstract: Genetic variations at the leptin receptor gene locus have been linked to diseases accompanying obesity and/or obesity-related diseases in different populations. However, the results from Previous studies have reported conflicting results. The aim of this study was to investigate whether LEPR gene SNP Gln223Arg (rs1137101) is associated with obesity and type II diabetes in Saudi adult women. Therefore, SNP rs1137101 in LEPR gene in a total of 425 women (150 obese diabetic, 130 obese non-diabetic, and 145 normal weight) was investigated using PCR and sequencing techniques. The genotype analysis of obese diabetic, obese non-diabetic, and normal weight revealed that the polymorphism seemed mainly confined to the first two groups of the cohort. In both obese non-diabetic and diabetic subjects, genotype distribution differ significantly from those expected under Hardy-Weinberg equilibrium conditions (obese non-diabetic, x2=132.6, P=0.0001; obese diabetic, x2=248.6, P=0.0001). In addition, there was no significant difference in the genetic distribution for rs1137101 polymorphism between obese non-diabetic and diabetic women (x2=0.01, P=0.92). The allele frequency for the polymorphism rs1137101 had a frequency of 0.09 in obese non- diabetic and 0.05 in obese diabetic females. As a conclusion, rs1137101 polymorphism of the LEPR gene is associated with susceptibility to obesity and type II diabetes. This polymorphism may represent genetic marker for the risk of obesity and type II diabetes. Running title: rs1137101polymorphism of the leptin receptor Key words: rs1137101 polymorphism, leptin receptor, obesity, type II diabetes. Introduction: Obesity is a very serious problem that has been a global epidemic since it has progressively increased over the past several decades. It is considered as a public health challenge because of its association with a numerous diseases and clinical disorders, including type II diabetes [1,2,3,4,5]. In the Kingdom of Saudi Arabia (KSA), few epidemiologic studies have been done to assess the prevalence of obesity and type II diabetes. The studies showed that the percentage of prevalence of obesity increased between 1997 and 2012 from 22.1 to 33.8% [6,7]. In 2011, among the Saudi population, the prevalence of diabetes was 34.1% in males and 27.6% in females [8]. The etiologies of obesity and diabetes in humans are complex and often involve an interaction of genetic and environmental factors. Work on obesity-related gene–environment interactions is still in its infancy. Having a better understanding of the genetic contributions to obesity and gene–environment interactions will generate a better understanding of the causal pathways that lead to obesity. Such knowledge could someday yield promising strategies for obesity prevention and treatment. Leptin receptor (LEPR) gene is a single- transmembrane-domain receptor of the cytokine- receptor family with widespread tissue distribution and several alternatively spliced isoforms [9,10]. Its product has defined a new biological pathway for the regulation of food intake and energy expenditure. The LEPR gene has been cloned [9] and mapped to 1p31 in humans [11]. Polymorphisms (SNPs) in the 20 exons and introns of LEPR gene have been identified [11,12,12,14,15,16,17,18]. A Common variant in exon 6 of LEPR is SNP rs1137101 that causes a change of glutamine to arginine at codon 223 [12]. The rs1137101 polymorphism is within the region encoding the extracellular domain of the leptin receptor and, therefore, the amino acid change affects all forms of the receptor. It has been shown that the LEPR rs1137101 polymorphism is associated with the variation in ligand binding; higher levels of ligand binding activity have been demonstrated in individuals homozygous for the G (LEPR Arg223Arg) allele than in carriers of the A (LEPR 223Gln) allele [19]). The frequency of this polymorphism was reported in many articles and was distinct in different ethnic groups. Some of these studies were conducted in the United States [11,14, 20, 21,22], Asia [17,23,24], Europe
  3. 3. International Journal of Medical Sciences and Health Care Vol-1 Issue-7 (Ijmshc-703) http://www.ijmshc.com Page 15 [16,19,25,26,27], and Oceania [28,29]. In the search of variants that could be important in the pathophysiology of human obesity, SNP rs1137101 has been investigated as possible factor [21,30,31,32,33,34,35]. Given the inconclusive nature of most studies published to date, it is necessary to perform further studies concerning this gene in other populations. So far, the Saudi populations have not been included in these studies. Motivated by the potential importance of rs1137101 polymorphism in obesity, this study aims to determine the relationship of rs1137101 polymorphism with obesity and type II diabetes. Methods Subjects Total of 425 women (150 obese diabetic, 130 obese non-diabetic, and 145normal weight) were selected for polymorphism screening. Diabetic obese women (BMI>30kg/m2 ) were recruited from diabetic patients attending a diabetic clinic at National Guard Hospital, Jeddah (KSA). Obese non-diabetic (BMI >30kg/m2 ) and positive controls (BMI<25kg/m2 ) were randomly chosen from individuals who volunteered for physical check-ups in the diabetic clinic at National Guard Hospital. All subjects signed a consent form after being informed of the purpose and procedures of the study. Females of ages 45-65 years were retained for the present study and younger age were excluded from the study. This cross-sectional study was conducted in the Department of Biochemistry Science College, King Abdul Aziz University, Jeddah, Saudi Arabia. The sequencing assay was done in King Faisal Specialist hospital and Research center, Riyadh, Saudi Arabia. Measurements For all the subjects, weight and height were measured by the same observer to the nearest 0.5kg and 0.5cm; respectively. Body mass index (BMI) was calculated as weight (kg) divided by height (m) squared. Subjects in this study were classified as normal weight (BMI< 25kg/m2 ), or obese (BMI> 30kg/m2 ). DNA extraction and genotyping DNA was extracted from whole blood using the procedure described in Ultraclean DNA isolation kit (USA), and used for subsequent analysis. The region containing the polymorphism was amplified by polymerase chain reaction (PCR) using primer pair previously described (Thompson et al., 1997). The reaction profiles consisted of an initial denaturation at 95o C for 15min, followed by 40 cycles at 95o C for 45sec, annealing at 60o C for 45sec, and extension at 72o C for 1min, with a final extention at 72o C for 10min. All PCR products were analyzed by agarose gel (2%) electrophoresis, purified, and sequenced by automated sequence analysis using Mega Bace/1000 DNA analysis system (Molecular Dynamics American Life Science, USA). Statistical analysis The allele frequencies of LEPR were tested for the Hardy-Weinberg equilibrium using the Chi-Square test. The same test was used in comparing genotype distributions of the rs1137101 polymorphism between obese non-diabetic, obese diabetic, and normal weight subjects. The level of significant was defined at P≤ 0.05. Results The amplification and the sequencing for exon 6 fragments were done for all the volunteers to screen for nucleotide variation in the second position of codon 223. The PCR products were electrophoreised on 2% agarose gel along with the DNA Molecular Weight Marker XIV (size range from100-1500 b), and showed sizes of 400bp (Figure 1). Upon sequencing of exon 6 of the LEPR gene, an A to G transition was found in obese non-diabetic women (17.3% variant frequency) and obese diabetic (9.7% variant frequency) at nucleotide 668 (codon 223). The transition caused an amino acid substitution; Glutamine was changed to Arginine (Gln223Arg). No sequence variants were found in the 145 normal weight individuals. Figure 2 shows the Sequence analysis of the rs1137101 variants of the amplified exon 6 of LEPR gene. The genotype distribution and allele frequencies for the rs1137101 polymorphism of the LEPR gene are presented in Table 1. In obese non-diabetic subjects, frequency of Gln223 and Arg223 alleles were 0.91 and 0.09 respectively. The genotype distributions deviate significantly from Hardy-Weinberg equilibrium (X2 =132.6; df =2; P=0.0001). In obese diabetic women, Gln223 and Arg223 allele frequencies were 0.95 and 0.05 respectively. The genotype distributions deviate significantly from Hardy-Weinberg equilibrium (X2 =249.6; df =2; P=0.0001). In comparing genotype distributions of the rs1137101 polymorphism between obese non-diabetic and obese diabetic subjects, Chi-Square test was used and showed no significant difference in the genetic distribution for rs1137101 polymorphism between obese non-diabetic and diabetic women (x2 =0.01, P=0.92). The genotype distribution of the rs1137101
  4. 4. International Journal of Medical Sciences and Health Care Vol-1 Issue-7 (Ijmshc-703) http://www.ijmshc.com Page 16 polymorphism was significantly different between the two groups and the normal weight subjects (X2 =9.3; df =1; P=0.002). These results imply a linkage of rs1137101 polymorphism with obesity and type II diabetes in Saudi women. Discussion Our results provide further support for the reported LEPR rs1137101polymorphism effect on the risk of obesity and type II diabetes, strengthening the notion that this interaction effect may possibly influence type II diabetes development. Genotype analysis of obese diabetic, obese non-diabetic, and normal weight revealed that the polymorphism seemed mainly confined to the first two groups of the cohort. Differences in genotype frequencies were observed between obese diabetic and obese non-diabetic women, but were not significant. The insignificant result does not rule out the possibility that the rs1137101 polymorphism may play a role in the progression toward the diabetic state. Type II diabetes, like obesity, is a polygenic disease and susceptibility to type II diabetes is influenced by a number of genes, each believed to have a small effect on disease development. We suggest that LEPR rs1137101polymorphism may exert a small effect on the disease. This result highlights the importance of examining rs1137101 polymorphism when assessing susceptibility to obesity and type II diabetes and supports the idea that obesity and type II diabetes can develop through key genes exerting minor effects. The striking finding was the extremely high occurrence of heterozygous genotype C/T at rs1137101 in exon 6 of the of the LEPR gene. The heterozygous and homozygous variant genotype showed that Gln/Arg percentage is higher than Arg/Arg percentage in both groups. This result does not rule out the possibility that variation in one allele may cause obesity and type II diabetes in combination with an as yet unidentified and/or not studied variation in other alleles. Our data is consistent with earlier studies that showed an association with obesity [11,19,21,36]. Thompson and co-workers were the first to report an association between Gln223Arg genotype and BMI in Pima Indians [11]. Similar results have been reported in postmenopausal Caucasian women [19], in the Brazilian populations [21] and in Mexican adolescents [36]. All studies indicated that carriers of the Arg allele have higher BMI, fat mass, and leptin levels than Gln homozygotes. In contrast to our results, other researchers have demonstrated a lack of association of this SNP with adiposity [20,22,37,38,39,]. There have been conflicting reports of association of rs1137101 polymorphism with obesity and type II diabetes. Investigators have pointed out reason for hiding the effect of rs1137101 polymorphism, and they relate that to the differences in the background variation in other genes among studied populations (11,12,21]. We suggest that the inconsistency in the results may be due to the type of obesity in the population studied, ethnicity, and/or the possibility that other SNPs within the leptin receptor may affect this data. Potential limitations of this study include its moderate size. However, the inclusion of only women of ages between 45 to 65 years provide a distinct advantage when performing genetic studies and evaluating the corresponding associations. In comparing allele frequency of the polymorphism investigated to the frequencies observed in several other ethnic populations, it showed that, obese non- diabetic women had a variant allele frequency (Arg 0.09) much lower than the rest of the other groups. In British, Quebec, American, French, Australian, Greek, and Danish showed homogenous frequencies (0.44, 0.45, 0.46, 0.44, 0.42, 0.32, and 0.43, respectively). On the other hand, Japanese, Pima, and Pacific Island of Nauruan were found to exhibit higher frequencies for Arg allele of the rs1137101 polymorphism. It has been suggested that the frequencies differ with ethnicity [40]. In that regard, we suggest that the cause of obesity in Saudi women may be uniquely different to the causes of these diseases in other populations. Also, persons with the Arg allele are more prone to obesity and type II diabetes. In conclusion, the results support the hypothesis of an effect of rs1137101 polymorphism on obesity and type II diabetes in humans. However, this effect does not seem to have a major impact on adiposity and type II diabetes in Saudi women. Additional functional studies to clarify the role of the rs1137101 polymorphism on leptin action in human metabolism are needed. Competing interests: The author declares that they have no competing interests. Acknowledgments: I thank all the participants for their generous cooperation. References: 1. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999; 341:1097-105.
  5. 5. International Journal of Medical Sciences and Health Care Vol-1 Issue-7 (Ijmshc-703) http://www.ijmshc.com Page 17 2. Callaham ST, Mansfield MJ. Type 2 diabetes mellitus in adolescents. CurropinPediatr 2000; 12:310- 315. 3. Antic V, Dulloo A, Montani JP. Multiple mechanisms involved in obesity-induced hypertension. Heart Lung Circ 2003; 12:84-93. 4. Yu Y, Lyons TJ. A lethal tetrad in diabetes: hyperglycemia, dislipidemia, oxidative stress, and endothelial dysfunction. AM J Med Sci 2005; 330: 227-232. 5. Xie B, Waters MJ, Schirra HJ. Investigating potential mechanisms of obesity by metabolomics. J Biomed Biotechnol 2012; 2012:805683. 6. Al-Nuaim AA, Bamgboye EA, Al-Rubeaan KA, Al- Mazrou Y. Overweight and obesity in Saudi Arabian adult population, role of socio-demographic variablesJ community Health 1997; 22(3): 211-223. 7. Habib SS. Body mass index and body fat percentage in assessment of obesity prevalence in Saudi adults. Biomed Environ Sci 2013; 26: 94-99. 8. Alqurashi KA, Aljabri KS, Bokhari SA. Prevalence of diabetes mellitus in a Saudi community. Ann Saudi Med 2011; 31:19-23. 9. Tartaglia LA, Dembski M, Weng X Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Wool EA, Monroe CA, Tepper RI. Identification and expression cloning of a leptin receptor, OB-R.Cell 1995; 83:1263-1271. 10. Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, Friedman JM. Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996; 379(6566):632-635. 11. Thompson DB, Ravussin E, Bennett PH, Bogardus C. Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians. Hum Mol Genet 1997; 6:675-679. 12. Considine RV, Considine EL, Williams CJ, Hyde TM, Caro JF.The hypothalamus leptin receptor in humans: identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations. Diabetes 1996; 9:992-994.Chagnon YC, Chung WK, Pérusse L, Chagnon M, Leibel RL, Bouchard C. Linkages and associations between the leptin receptor (LEPR) gene and human body composition in the Québec Family Study. Int J Obes 1999; 23:278–286. 13. Chung WK, Power-Kehoe L, Chua M, Lee R, Leibel RL. Genomic structure of the human OB receptor and the identification of two novel intronic microsatellites.Genome Res 1996; 6:1192-1199. 14. Chung WK, Power-Kehoe L, Chua M, Chu F, Aronne L, Huma Z, Sothern M, Udall JN, Kahle B, Leibel RL. Exonic and intronic variation in the leptin receptor (OBR) of obese humans.Diabetes 1997; 46:1509-1511. 15. Francke S, Clement K, Dina C, Inoue H, Behn P, Vatin V, Basdevant A, Guy-Grand B, Permutt MA, Froguel P, Hager J. Genetic studies of the leptin receptor gene in morbidly obese French Caucasian families. Hum Genet 1997; 100:491-496. 16. Gotoda T, Manning BS, Goldstone AP, Imrie H, Evans AL, Strosberg AD, McKeigue PM, Scott J, Aitman TJ. Leptin receptor gene variation and obesity: lack of association in a white British male population. Hum Mol Genet 1997; 6:869-876. 17. Matsuoka N, Ogawa Y, Hosoda K, Matsuda J, Masuzaki H, Miyawaki T, Azuma N, Natsui K, Nishimura H, Yoshimasa Y, Nishi S, Thompson DB, Nakao K. Human leptin receptor gene in obese Japanese subjects: evidence against either obesity- causing mutations or association of sequence variants with obesity. Diabetologia 1997; 40:1204-1210. 18. Oksanen L, Kaprio J, Mustajoki P, Kontula K. A common pentanucleotide of the 3’- untranslated part of the leptin receptor gene generates a putative stem-loop motif in the mRNA and is associated with serum insulin levels in obese individuals. Int J Obes 1998; 22:634-640. 19. Quinton ND, Lee AJ, Ross RJM, Eastell R, Blakemore AIF. A single nucleotide polymorphism in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian women. Hum Genet 2001; 108:233-236. 20. Silver K, Walston J, Chung WK, Yao F, Parikh VV, Andersen R, Cheskin LJ, Elahi D, Muller D, Leibel RL, ShuldinerAR.The Gln223Arg and Lys656Asn polymorphisms in the human leptin receptor do not associate with traits related to obesity. Diabetes 1997; 46:1898-1900. 21. MatteviVS,ZembrzuskiVM,Hutz MH. Association analysis of genes involved in the leptin-signaling
  6. 6. International Journal of Medical Sciences and Health Care Vol-1 Issue-7 (Ijmshc-703) http://www.ijmshc.com Page 18 pathway with obesity in Brazil.Int J ObesRelatMetabDisord 2002; 26(9):1179-1185. 22. Stefan N, Vozarova B, Del Parigi A, Ossowski V, Thompson DB, Hanson RL, Ravussin E, Tataranni PA. The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism. Int J ObesRelatMetabDisord 2002; 26:1629-1632. 23. Endo K, Yanagi H, Hirano C, Hamaguchi H, Tsuchiya S, Tomura S. Association of Trp64arg polymorphism of the beta3-adrenergic receptor gene and no association of Gln223Arg polymorphism of the leptin receptor gene in Japanese schoolchildren with obesity. Int J ObesRelatMetabDisord 2000; 24:443- 449. 24. Koh JM, Kim DJ, Hong JS, Park JY, Lee KU, Kim SY, Kim GS. Estrogen receptor alpha gene polymorphisms Pvu II and Xba I influence association between leptin receptor gene polymorphism (Gln223Arg) and bone mineral density in young men. Eur J Endocrinol 2002; 147:777-783. 25. Echwald SM, Sorensen TD, Sorensen TI, Tybjaerg-Hansen A, Andersen T, Chung WK, Leibel RL, Pedersen O. Amino acid variants in the human leptinreceptor:lack of association to juvenile onset obesity. BiochemBiophys Res Commun 1997; 233:248-252. 26. Rosmond R, Chagnon YC, Holm G, Chagnon M, Perusse L, Lindell K, Carlsson B, Bouchard C, Bjorntorp P. Hypertension in obesity and the leptin receptor gene locus. J ClinEndocrMetab 2000; 85:3126-3131. 27. Mammes O, Aubert R, Betoulle D, Pean F, Herbeth B, Visvikis S, Siest G, Fumeron F. LEPR gene polymorphisms: associations with overweight, fat mass and response to diet in women. Eur J Clin Invest 2001; 31:398-404. 28. de Silva AM, Walder KR, Aitman TJ, Gotoda T, Goldstone AP, Hodge AM, de Courten MP, Zimmet PZ, Collier GR. Combination of polymorphisms in OB-R and the OB gene association with insulin resistance in Nauruan males. Int J ObesRelatMetabDisord 1999; 23:816-822. 29. de Silva AM, Walder KR, Boyko EJ, Whitecross KF, Nicholson G, Kotowicz M, Pasco J, Collier GR. Genetic variation and obesity in Australian women. Obes Res 2001; 19:733-740. 30. van Rossum CT, Hoebee B, Seidell JC, Bouchard C, van Baak MA, de Groot CP, Chagnon M, de Graaf C, Saris WH. Genetic factors as predictors of weight gain in young adult Dutch men and women. Int J ObesRelatMetabDisord 2002; 26:517-528. 31. Salopuro T, Pulkkinen L, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Tuomilehto J, Laakso M, Uusitupa M; Finnish Diabetes Prevention Study Group. Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: The Finnish Diabetes Prevention Study. Int J Obes (Lond) 2005; 29(10):1245-1251. 32. Chen Z, Guo DS, Li Y, Kong XY, Guo M, Wu YF. Sttudy on the relationship between Gln223Arg variant in leptin receptor gene and obesity.Zhonghua Liu Xing Bing XueZaZhi 2006; 27(12): 1078-1081. 33. Fairbrother UL, Tanko LB, Walley AJ, Christiansen C, Froguel P, Blakemore AI. Leptin receptor genotype at Gln223Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women. J Bone Miner Res 2007; 22(4):544-550. 34. Marti A, Santos JL, Gratacos M, Moreno-Aliaga MJ, Martinez JA, Estivill X. Association between leptin receptor (LEPR) and brain-derived neurotrophic factor (BDNF) gene variants and obesity: a case-contol study. NutrNeurosci 2009; 12(4): 183-188. 35. Yang GP, Peng SH, Zuo SY, Wang YR, Peng XN, Zeng XM. Meta-analysis on the relationship between leptin receptor Gln223Arg and Pro1019Pro gene polymorphism and obesity in the Chinese population.Zhonghua Liu Xing Bing XueZaZhi, 2011;32(10):1037-42 36. Guizar-Mendoza JM, Amador-Licona N, Flores- Martinez SE, Lopez-Cardona MG, Ahuatzin-Tremary R, Sanchez-Corona J. Association analysis of the Gln223Arg polymorphism in the human leptin receptor gene, and traits related to obesity in Mexican adolescents. J Hum Hypertens 2005; 19:341-346. 37. Chagnon YC, Wilmore JH, Borecki IB, Gagnon J, Perusse L, Chagnon M, Collier GR, Leon AS, Skinner JS, Rao DC, Bouchard C. Associations between the leptin receptor gene and adiposity in middle-aged Caucasian males from the HERITAGE family study. J ClinEndocrinolMetab 2000; 85: 29-34.
  7. 7. International Journal of Medical Sciences and Health Care Vol-1 Issue-7 (Ijmshc-703) http://www.ijmshc.com Page 19 38. Heo M, Leibel RL, Boyer BB, Chung W, Koulu KM, Karvonen MK, Pesonen U, Rissanen A, Laakso M, Uusitupa MIJ, Chagnon Y, Bouchard C, Donohoue PA, Burns TL, Shuldiner AR, Silver K, Andersen RE, Pedersen O, Echwald S, Sorensen T I A, Behn P, Permutt M A, Jacobs KB, Elston RCD, Hoffman J, Allison DB. Pooling Analysis of Genetic Data: The Association of Leptin Receptor (LEPR) Polymorphisms With Variables Related to Human Adiposity. Genetics 2001; 159:1163 - 1178. 39. Mergen H, Karaasian C, Mergen M, DenizOzsoy E, Ozata M. LEPR, ADBR3, IRS-1 and 5-HTT genes polymorphisms do not associate with obesity. Endocr J 2007; 54: 89-94. 40. Chagnon YC, Chung WK, Pérusse L, Chagnon M, Leibel RL, Bouchard C. Linkages and associations between the leptin receptor (LEPR) gene and human body composition in the Québec Family Study. Int J Obes 1999; 23:278–286. Figure 1 :Amplification of theexon 6 of LEPR gene by PCR. Lane M: molecular weight marker (100bpladder). Lanes 1-16: the amplified exon 6 fragments (size of 400bp(
  8. 8. International Journal of Medical Sciences and Health Care Vol-1 Issue-7 (Ijmshc-703) http://www.ijmshc.com Page 20 Figure 2: Sequence analysis of the rs1137101 variants of the amplified exon 6 of the LEPR gene. Table 1: Genotype and Allele frequencies of rs1137101 polymorphism in obese non-diabetic and diabetic Saudi women. Group Gln/Gln Gln/Arg Arg/Arg Gln223 Arg223 Obese non- diabetic (n=130) 0.600 (60.0%) 0.308 (30.8%) 0.092 (9.2%) 0.91 0.09 Obese diabetic (n=150) 0.613 (61.3%) 0.333 (33.3%) 0.053 (5.3%) 0.95 0.05

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