Analyzing the Impact of FSHR Variants on Polycystic Ovary Syndrome-a Case-Control Study in Punjab.

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic syndrome that involves hyperandrogenism, menstrual irregularities, and/or small cysts in one or both ovaries which might lead to infertility in women. The genetics of PCOS is heterogenous with the involvement of several genes reported in the hypothalamic-pituitary-gonadal axis. Follicular growth and steroidogenesis regulation are both critically dependent on follicle-stimulating hormone (FSH). The variants of FSHR cause abnormal folliculogenesis, steroidogenesis, and oocyte maturation at various stages of growth and may render women more susceptible to PCOS development. The present case-control study evaluated the association of FSHR rs6165 and rs6166 variants with PCOS. A total of 743 females were recruited. PCR-RFLP method was used for the genotypic analysis of FSHR polymorphisms. Obesity was examined according to the categorization of body mass index (BMI) and waist-hip ratio (WHR). Biochemical analysis, including a lipid profile, LH, FSH, and testosterone levels, was done in both PCOS women and controls. BMI and WHR revealed a statistically significant difference between PCOS cases and controls. Overall, levels of HDL were significantly lower, whereas cholesterol, triglycerides, LDL, and VLDL levels were higher in PCOS women (p < 0.05). The genotypic and allelic frequencies of rs6165 and rs6166 did not demonstrate significant differences when PCOS women were compared with the control group. However, clinical features of PCOS including gonadotropic hormone (FSH), hyperandrogenism, and dyslipidemia were significantly correlated with variants of FSHR. The present study concludes that rs6165 and rs6166 were significantly related to clinical features of PCOS, regardless of providing direct disease risk.

Association analysis of LHCGR variants and polycystic ovary syndrome in Punjab: a case-control approach.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that affects women at their child bearing age. The exact etiology is uncertain, however the involvement of multiple genes and environmental interactions has been proposed for the advancement of PCOS. The aim of present study was to evaluate the association of LHCGR variants (rs2293275 and rs12470652) with PCOS in Punjab. METHODS: The present case-control study comprised a total of 743 women (421 PCOS cases and 322 healthy controls). Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). Biochemical analysis was carried out to measure the levels of cholesterol, High-density lipoprotein (HDL), Low-density lipoprotein (LDL), Very low-density lipoprotein (VLDL), triglycerides, testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). All the statistical analysis was done using SPSS (version21, IBM SPSS, NY, USA). RESULTS: The mutant genotype (AA) and mutant allele (A) of rs2293275 conferred 1.7 and 1.3 fold risk, respectively and mutant allele (C) of rs12470652 conferred 2.3 fold risks towards PCOS progression. Levels of cholesterol and triglycerides were elevated and HDL levels were lower in PCOS cases as compared to controls. Total testosterone and luteinizing hormone levels were also found to be higher in PCOS cases. CONCLUSION: Our study postulated that LHCGR variants are playing a cardinal role in the progression of PCOS and can be used to assess the risk of PCOS in women of reproductive age.

Association Analysis of CYP11A1 Variants with Polycystic Ovary Syndrome: a Case-Control Study from North India.

The most common multifactorial endocrine disorder in females of reproductive age is polycystic ovary syndrome (PCOS), affecting about 5-10% of females worldwide and 9.3% of females in India. Androgen excess in PCOS is caused as a result of defects in steroidogenesis genes. CYP11A1 is an imperative marker in the steroid synthesis pathway, and the altered expression of CYP11A1 has been reported to disrupt the synthesis of steroids and hence conferring risk for the development of PCOS. The present study aimed to analyze genetic variants (rs11632698, rs4077582, rs4887139) of CYP11A1 with PCOS from North India. The study included 270 PCOS females diagnosed according to Rotterdam 2003 criteria and 270 age-matched healthy non-PCOS females. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for the genotypic analysis of the selected genetic variants. Association analysis of biochemical parameters (cholesterol, triglyceride, high-density lipoprotein) and anthropometric measurements with PCOS cases was done. The genetic variants of CYP11A1 (rs11632698, rs4077582, and rs4887139) demonstrated significant association with PCOS cases (p=1.0E-12, p=3.0E-3, p=1.0E-2, respectively). Binary logistic regression revealed that the dominant model of rs11632698 conferred 2.0 risk, and dominant as well as the co-dominant model of rs4887139 conferred risk of 2.2 and 2.4 fold, respectively, towards the progression of PCOS. The overall mean triglyceride levels were elevated, and mean HDL levels were lower in PCOS cases as compared to threshold values. The significant association of studied genetic variants suggested the important role of CYP11A1 in susceptibility to PCOS. The study was the first of its kind from our region and provided baseline data of genetics of PCOS.

Genetic association study from North India to analyze association of CYP19A1 and CYP17A1 with polycystic ovary syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS) is a complex multifactorial endocrine disorder affecting approximately 5-10% of women of reproductive age. Affected women have menstrual disturbances due to anovulation, infertility, and hyperandrogenism. Ovarian androgen overproduction is the key physiopathologic feature of PCOS. A number of genes encoding major enzymes of the androgen metabolic pathways, such as HSD17B6, CYP19A1, CYP11A1, CYP17A1, and INSR, have been examined. Very few studies have been done in North India. There is an increasing prevalence of PCOS in women in Punjab and it is the leading cause of female infertility. In view of the strong evidence implicating the importance of CYP19A1 and CYP17A1 in androgen metabolic pathways, we investigated the association of rs700519, rs2414096, and rs743572 (- 34T>C) polymorphisms on susceptibility of developing PCOS, in North India. METHODS: A total of 500 subjects (women of reproductive age) including 250 PCOS cases and 250 healthy age-matched controls were included in the present study. DNA was extracted from venous blood for all samples, and association analysis for rs2414096, rs700519, and rs743572 was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Lipid profile was done using a biochemical analyzer and body mass index (BMI) was measured for all cases. Statistical analysis was performed. RESULTS: Significant association of - 34T>C polymorphism of CYP17A1 was found with PCOS (p = 0.0005). BMI was statistically different between PCOS cases and controls (p = 0.000). Triglycerides were high in PCOS women. Variations of CYP19A1 were not statistically significant with PCOS. CONCLUSIONS: These data suggest that - 34T>C polymorphism in CYP17A1 is associated with PCOS in North India. No polymorphism of CYP19A1 was found to be associated.