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

CAPN10 haplotype effect: Haplotypic OR by comparison to the reference with its 95% CI.

*<p>(in comparison to the reference haplotype 11121).</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

CAPN10 haplotype frequency distribution among PCOS cases and controls.

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

Pairwise LD estimates in PCOS cases and controls. Data are D′ values.

<p>Pairwise LD estimates in PCOS cases and controls. Data are D′ values.</p

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

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

Primers used for CAPN10 polymorphism genotyping.

<p>Primers used for CAPN10 polymorphism genotyping.</p