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Understanding the Genetics and Treatment of Polycystic Ovarian Syndrome (PCOS
- 1. Polycystic ovarian syndrome • Presented by : Simran Shabir • MSc Biotechnology (2nd Sem) • Roll no. : 04 • Presented to : Dr Anita Yadav KURUKSHETRA UNIVERSITY, HARYANA PCOS
- 2. • Introduction • Prevalence • Diagnosis • Pathophysiology • Clinical presentations • Syndromes associated long term complications • Hormonal diagnosis ❖ Biotechnology and PCOS • Paper 1 • Paper 2 • Paper 3 • Conclusion • References
- 3. • PCOS is a lifelong multifactorial disorder where ➢Individual genes ➢Gene-gene interaction or ➢Gene-environment interactions have been reported to influence pre-disposition to PCOS development.
- 4. • The worldwide prevalence of PCOS is estimated to be 5-10%. • Association of PCOS with infertility is 40%. • A significant difference was noted in white and black females, i.e., 8% and 4%, respectively in Caucasian and Black races. • PCOS is also quite prevalent in Indian females of reproductive age, at nearly 9.13% PCOS is diagnosed by criteria set by the National Institutes of Health (NIH) in 1990 and the estimation of the prevalence of PCOS depends on how many of the criteria were followed. Prevalence
- 5. 1) Oligomenorrhea or anovulatory cycle Clinical or biochemical 2) Hyperandrogenism •Acne •Hirsutism •Elevated Sr. Testosterone levels 3) USG --> 12 follicles (2-9 mm diameter) arranged peripherally Rotterdam criteria Any 2 positive criteria indicates PCOS Diagnosis of PCOS
- 6. Classical image of PCOS
- 7. Why does PCOS occur? Why people have PCOS?
- 8. Defective aromatisation in ovary • Estradiol (E2) Theca cell hypertrophy • Androgen Normal peripheral aromatisation • Estrone (E1) Pathophysiology of PCOS
- 9. Androgen LH FSH aromatase Estrogen Androgen Granulosa cell Theca cell 2 cell – 2 gonadotrophin theory
- 10. Aromatisation of androgen a) Ovary Estradiol (E2) b) Peripheral Estrone (E1)
- 11. Hyper-estrogenic state Stein-Leventhal Syndrome Other names for PCOS
- 12. How these three basic problems lead to anovulation?
- 14. Amenorrhoea/ Oligomenorrhoea Hirsutism/ Acne Infertility Obesity Insulin resistance Clinical presentations
- 15. Hyper Androgenism Insulin Resistance Acanthosis Nigricans HAIR-AN SYNDROME Syndromes associated with PCOS
- 17. Long term complications associated with PCOS Diabetes mellitus type (II) Endometrial hyperplasia &Endometrial carcinomas Breast carcinoma Osteoporosis Cardiovascular diseases Syndrome X Hypertension
- 18. Investigation and Diagnosis Rotterdam's Criteria 2 hours OGTT to be done.
- 19. INCREASED LEVELS DECREASED LEVELS LH FSH Androgen (total & free testosterone) Estrone (E2) Estradiol (E1) Insulin & IGF-1 Sex hormone binding globulin Progesterone LDL , Triglycerides HDL Prolactin Hormonal Changes
- 22. Abstract Bioinformatic tools Modeller 9v14 and Ab-initio programs 43 proteins identified Phylogenetic analysis Microarray data analysis R programming
- 23. Genetics of PCOS List of 43 genes involved in PCOS with UniProt-ID , PDB-ID and chromosomal locations
- 25. Modelled structure of proteins related to PCOS using Modeller 9v14 and Ab-initio programs
- 28. Relatedness of the 43 protein-coding genes analysed using Clustral Omega
- 29. Unrooted phylogenetic tree representing 43 genes
- 30. Result 14 genes were identified and retrieved from NCBI and UniProt 8 were up-regulated genes 6 were down-regulated genes
- 31. • Computational study of genetic disorders like PCOS can be scrutinised in both ➢Sequential aspect and ➢Structural aspect to cognise the mechanism of such types of genetic syndrome. Conclusion
- 33. Abstract CYP19A1 gene Encodes an aromatase enzyme that mediate conversion of androgens to Estrogen. 3 genetic variants investigated: Exonic variant – rs700519 Two intronic variants- rs2414096 & rs60271534
- 34. Introduction CYP1PA1 gene encoding aromatase is located on Chr.15q21.1 Spans more than 123kb – 30kb – coding region 93kb – regulatory region Nine alternate untranslated exons present in 93kb gene regulatory region regulate the specificity.
- 35. Genetics In silico analysis & multiple logistic regression analysis
- 36. Result 1) • All the 3 gene variants are associated significantly with disease susceptibility (p<0.05). 2) • Exonic variant - Arg264Cys has a major role in the disease pathogenicity through its reduced aromatase activity.
- 39. 1) Genes involved in Ovarian and Adrenal Steroidogenesis CYP11a CYP21 CYP17 CYP19 Cholesterol Progesterone Enzyme coded by CYP11a 17- hydroxyprogesterone 11-deoxycortisol Enzyme coded by CYP21 Pregnenolone & progesterone 17- hydroxypregnelone & 17- hydroxyprogesterone Enzyme coded by CYP17 Enzyme aromatase p450 Formation of Estrogen
- 40. Dietary therapy OCPs LOD ART Current state of treatment
- 41. Conclusion PCOS is a life-long disorder. PCOS is a multi-functionary disorder. No consensus has been reached on an established genitive marker for PCOS. Progress have been achieved in the management and diagnosis of PCOS ; however, not significant is known about the molecular players and signalling pathway underlying.
- 42. References 1. https://www.researchgate.net/publication/282050161_Polycystic_ovary_syndrome_Ro le_of_aromatase_gene_variants_in_South_Indian_women 2. https://pubmed.ncbi.nlm.nih.gov/27114910/ 3. https://www.dovepress.com/genetic-basis-of-polycystic-ovary-syndrome-pcos-current- perspectives-peer-reviewed-fulltext-article-TACG 4. https://www.youtube.com/watch?v=slBzDA_3JZI
- 43. Thank you