Polymorphisms and haplotypes of insulin-like factor 3 gene are associated with risk of polycystic ovary syndrome in Indian women.

Abstract Background Insulin-like factor 3 (INSL3), secreted by the ovarian theca cells is involved in androgen production, follicular growth and oocyte maturation. Both androgens and INSL3 levels are reported to be elevated in women with polycystic ovary syndrome (PCOS), indicating that INSL3 could contribute to PCOS etiology. This case–control association study explored the impact of INSL3 polymorphisms on PCOS susceptibility and its related traits. Methods Genotyping of exonic polymorphisms of INSL3 was performed in controls (n = 333) and PCOS (n = 405) women. Phenotyping (clinical, biochemical and hormonal parameters) was carried out in 205 controls and 301 PCOS women. Genotype, haplotype and genotype–phenotype associations were determined using statistical tests. Results Three polymorphisms in exon 1- rs2286663 (G/A), rs1047233 (A/G), and rs6523 (A/G), and one in exon 3- rs1003887 (G/A), were present in our study subjects. The frequencies of rs6523 and AGAG haplotype were significantly increased in PCOS women. The rs6523 polymorphism showed significant association with increased cholesterol and HDL-C levels in PCOS women while in controls with decreased FBS, Bio-T and FAI, and increased SHBG levels. Significant association of, rs1047233 polymorphism with improved androgen related parameters in controls, rs2286663 polymorphism with decreased QUICKI in PCOS and rs1003887 polymorphism with increased insulin levels and HOMA-IR in controls were observed. Conclusions The rs6523 polymorphism and AGAG haplotype of INSL3 showed significant association with increased risk of PCOS. Additionally, INSL3 polymorphisms influenced metabolic and hyperandrogenemia related parameters in both controls and PCOS women. This is the first study to suggest that INSL3 may be a genetic predisposition factor in PCOS pathophysiology.