Polycystic ovary syndrome (PCOS) is a common endocrine disorder predominantly affecting women of reproductive age. Clinical manifestations are diverse including hyperandrogenism, anovulation, infertility and increased risk of metabolic diseases besides psychosocial dysfunction. This review provides information on the problem of PCOS in India, its pathophysiology, genetics and an overview of current management options to instigate further research in this field. Prevalence of PCOS in India ranges from 3.7 to 22.5 per cent depending on the population studied and the criteria used for diagnosis. Abnormalities in leptin-adiponectin (adipocyte biology), oxidative stress and autoimmunity are among the mechanisms studied regarding pathogenesis of PCOS. Many candidate gene studies have shown associations with PCOS in various studies. Studies have consistently demonstrated the relationship between the well-known manifestation of hyperandrogenism among Indian PCOS women and the metabolic morbidities including insulin resistance, glucose intolerance and cardiovascular risk. Management of individual components of PCOS can be achieved by medications or surgical methods, though further clarification regarding pathogenesis of PCOS is needed to sharpen our therapeutic armamentarium.

Epidemiology, pathogenesis, genetics & management of polycystic ovary syndrome in India.

No detectable association of IGF2BP2 and SLC30A8 genes with type 2 diabetes in the population of Hyderabad, India

Summary Polycystic Ovary Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a heterogeneous androgen excess disorder determined by the interaction of multiple genetic and environmental factors. Our earlier analysis on a panel of six candidate genes (Androgen receptor CAG repeats, Follistatin, Luteinizing hormone β subunit, Calpain10, Insulin receptor substrate-1 and PPARγ) based on 250 PCOS cases and 299 controls revealed significant association patterns with PCOS among South-Indian women. We report here for the first time, the SNP-SNP and SNP-environment interactions of these genes in the same cohort. Both multivariate logistic regression as well as epistasis analysis (using Multifactor dimensionality reduction software) yielded significant results (P < 0.05). All CAPN10 SNPs show association (either risk-conferring or protective) in the obese group, highlighting the importance of this gene in the PCOS pathophysiology. LHP7(LHβ) and UCSNP44(CAPN10) emerged to be the prominent SNPs in the SNP-SNP interaction analysis. The best SNP-SNP interaction model was obtained between CAPN10 UCSNP-44 and PPARγ His447His, implying a significant metabolic component in the PCOS pathology. Replicating our findings in BMI-specific cohorts in different ethnic populations would be warranted in future to identify the physiological networks in PCOS.

The role of epistasis in the etiology of Polycystic Ovary Syndrome among Indian women: SNP-SNP and SNP-environment interactions.

Objective(s): Polycystic ovary syndrome (PCOS) is an endocrinopathy in women, which, unlike its impact on fertility and health of women, there is no clear understanding about the causal mechanisms of this pathogenesis. The aim of this review paper is to investigate the pathophysiological pathways affecting the PCOS etiology, based on functions of gonadotropins– and steroid hormones–related genes.Materials and Methods: Due to different hormonal and metabolic signs of this complex disorder, different hypotheses are mentioned about etiology of this syndrome. Because of the heterogeneity of the reasons given for this syndrome and the spread of the effective genes in its pathophysiology, most of genes affected by sex-related hormonal imbalances are examined for discriminative diagnosis. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women in peer-reviewed journals in PubMed and Google Scholar databases were included in this review.Results: In previous studies, it has been well demonstrated that PCOS in some individuals have a genetic origin. Pathophysiological functions of genes are primarily responsible for the synthesis of proteins that have role in PCOS before hyperandrogenism including GnRHR, FSHβ, FSHR, LHCGR, CYP19A1, HSD17B, AR and SHBG, and their effects in PCOS of human have been confirmed.Conclusion: Hormonal imbalances are the first reason mentioned in PCOS etiology, and usually characterized with menstrual irregularities in PCOS women. Hyperandrogenism and gonadotropin secretion disorders are shown in PCOS condition, which are related to steroidogenesis pathways and hypothalamic–pituitary–ovarian axis disturbances, respectively.

https://ijbms.mums.ac.ir/article_11818_f1883fb631e6dde9fbfcbbae1c54b742.pdf

Pathophysiological mechanisms of gonadotropins- and steroid hormones-related genes in etiology of polycystic ovary syndrome.

Impaired ovarian follicle development, the hallmark of polycystic ovarian syndrome (PCOS), is believed to be due to the changes in expression of related genes such as follistatin (FST).Expression of FST gene and methylation level of its promoter in theca cells from adult female rats, prenatally exposed to androgen excess, during different phases of the estrus cycle was determined and compared with controls.Eight pregnant Wistar rats (experimental group) were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n = 8) received 500 ml solvent. Based on observed vaginal smear, adult female offspring of mothers were divided into three groups. Levels of serum steroidogenic sexual hormones and gonadotropins, expression and promoter methylation of the FST gene were measured using ELISA, cyber-green real-time PCR and bisulfite sequence PCR (BSP), respectively.Compared to controls, the relative expression of FST gene in the treated group decreased overall by 0...

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Alteration in follistatin gene expression detected in prenatally androgenized rats.

Background: Out of a panel of 37 candidate genes tested for linkage with polycystic ovary syndrome (PCOS), the strongest evidence of linkage was reported in the follistatin (FST) gene region. Subsequently, a couple of studies outside India investigated the FST gene for the presence of any mutations and its association with PCOS and the results were found to be largely inconsistent probably due to differences in the ethnic backgrounds and small sample sizes. Aims: To screen the FST gene for mutations and to establish their association pattern with PCOS among a large cohort of South Indian women. Settings and Design: Case-control study. Materials and Methods: PCOS cases were recruited according to the 2003 Rotterdam diagnostic criteria. All the exons of the FST gene were amplified and analyzed in all the cases and controls for the presence of mutations using polymerase chain reaction (PCR) and direct DNA sequencing. Results: A total of 549 women consisting of 250 PCOS cases and 299 controls were recruited for the study. No mutations were found in any of the exons of the FST gene in our Indian sample which is consistent with an earlier finding among the Asian women from Singapore. Although three of the four cohorts of Caucasian background studied earlier reported variants, none of them could establish a strong association with PCOS. Conclusions: The occurrence of the exonic variants of FST gene seems to be dependent on the ethnic background of the subjects under study and its role in the PCOS pathophysiology cannot be established with hitherto available evidence.

M B Reddy

Papers

Does follistatin gene have any direct role in the manifestation of polycystic ovary syndrome in Indian women