Androgen Receptor CAG Repeat Polymorphism and Epigenetic Influence among the South Indian Women with Polycystic Ovary Syndrome

The present study was carried out to assess the role of androgen receptor CAG repeat polymorphism and X chromosome inactivation (XCI) pattern among Indian PCOS women and controls which has not been hitherto explored and also to test the hypothesis that shorter CAG alleles would be preferentially activated in PCOS. CAG repeat polymorphism and X chromosome methylation patterns were compared between PCOS and non-PCOS women. 250 PCOS women and 299 controls were included for this study. Androgen receptor CAG repeat sizes, XCI percentages, and clinical and biochemical parameters were measured. The mean CAG repeat number is similar between the cases (18.74±0.13) and controls (18.73±0.12). The obese PCOS women were significantly more frequent in the <18 and >20 CAG repeat category than the lean PCOS women, yielding a highly significant odds (p = 0.001). Among the women with non-random X-inactivation, alleles with <19 repeats were more frequently activated among cases than controls (p = 0.33). CAG repeat polymorphism by itself cannot be considered as a useful marker for discriminating PCOS. We observed a trend of preferential activation of the shorter allele among the PCOS cases with non random XCI pattern. In the obese PCOS women, this microsatellite variation may account for the hyperandrogenicity to a larger extent than the lean PCOS women

Role of Progesterone Receptor Polymorphisms in the Recurrent Spontaneous Abortions: Indian Case

Background: We attempt to ascertain if the 3 linked single nucleotide polymorphisms (SNPs) of the Progesterone Recepto

Association of CAPN10 SNPs and Haplotypes with Polycystic Ovary Syndrome among South Indian Women

Polycystic Ovary Syndrome (PCOS) is known to be characterized by metabolic disorder in which hyperinsulinemia and peripheral insulin resistance are central features. Given the physiological overlap between PCOS and type-2 diabetes (T2DM), and calpain 10 gene (CAPN10) being a strong candidate for T2DM, a number of studies have analyzed CAPN10 SNPs among PCOS women yielding contradictory results. Our study is first of its kind to investigate the association pattern of CAPN10 polymorphisms (UCSNP-44, 43, 56, 19 and 63) with PCOS among Indian women. 250 PCOS cases and 299 controls from Southern India were recruited for this study. Allele and genotype frequencies of the SNPs were determined and compared between the cases and controls. Results show significant association of UCSNP-44 genotype CC with PCOS (p = 0.007) with highly significant odds ratio when compared to TC (OR = 2.51, p = 0.003, 95% CI = 1.37–4.61) as well as TT (OR = 1.94, p = 0.016, 95% CI = 1.13–3.34). While the haplotype carrying the SNP-44 and SNP-19 variants (21121) exhibited a 2 fold increase in the risk for PCOS (OR = 2.37, p = 0.03), the haplotype containing SNP-56 and SNP-19 variants (11221) seems to have a protective role against PCOS (OR = 0.20, p = 0.004). Our results support the earlier evidence for a possible role of UCSNP-44 of the CAPN10 gene in the manifestation of PCOS

Role of Androgen Receptor CAG Repeat Polymorphism and X-Inactivation in the Manifestation of Recurrent Spontaneous Abortions in Indian Women

The aim of the present study was to investigate the role of CAG repeat polymorphism and X-chromosome Inactivation (XCI) pattern in Recurrent Spontaneous Abortions among Indian women which has not been hitherto explored. 117 RSA cases and 224 Controls were included in the study. Cases were recruited from two different hospitals - Lakshmi Fertility Clinic, Nellore and Fernandez Maternity Hospital, Hyderabad. Controls were roughly matched for age, ethnicity and socioeconomic status. The CAG repeats of the Androgen Receptor gene were genotyped using a PCR-based assay and were analysed using the GeneMapper software to determine the CAG repeat length. XCI analysis was also carried out to assess the inactivation percentages. RSA cases had a significantly greater frequency of allele sizes in the polymorphic range above 19 repeats (p = 0.006), which is the median value of the controls, and in the biallelic mean range above 21 repeats (p = 0.002). We found no evidence of abnormal incidence of skewed X-inactivation. We conclude that longer CAG repeat lengths are associated with increased odds for RSA with statistical power estimated to be ∼90%

CAPN10 haplotype frequency distribution among PCOS cases and controls.

*<p>Standard Pearson chi square value with degree of freedom = 1.</p

Minor allele frequencies of CAPN10 markers in different populations.

a<p>Horikawa <i>et al.</i> (2000).</p>b<p>Vollmert <i>et al.</i> (2007).</p>c<p>Evans <i>et al.</i> (2001).</p>d<p>Gonzalez <i>et al.</i> (2004).</p>e<p>Cassell <i>et al.</i> (2002).</p>f<p>Bodhini <i>et al.</i> (2010).</p>g<p>Adak <i>et al.</i> (2010).</p>h<p>Present study.</p

Clinical profile of the PCOS cases under study.

*<p>significantly different between lean PCOS and obese PCOS cases (p≤0.002).</p>**<p>Given the lean body mass of Indian women (Asian Indian Phenotype), BMI≥25 is generally considered as cut off distinguishing the lean women from overweight/obese women albeit the WHO criteria specifies BMI>30 as obese.</p

Linkage disequilibrium plot for CAPN10 polymorphisms in the entire cohort of PCOS cases and controls.

<p>D′ values are mentioned in the LD blocks.</p

Logistic regression analysis of UCSNP-44 for association with PCOS, taking age and BMI as covariates.

@<p>CI – Confidence interval.</p

Genotype frequency distribution of CAPN10 polymorphisms among PCOS cases and controls.

*<p>Standard Pearson chi square value with degree of freedom = 2.</p>#<p>Del – Deletion.</p><p>Ins – Insertion.</p