Polycystic ovary syndrome is associated with genetic polymorphism in the insulin signaling gene IRS-1 but not ENPP1 in a Japanese population

Abstract Recent studies indicate that insulin resistance resulting from altered post-receptor signaling is associated with polycystic ovary syndrome (PCOS). We hypothesized that insulin receptor substrate-1 ( IRS-1 ) Gly972Arg polymorphism and/or ectonucleotide pyrophosphatase/phosphodiesterase 1 ( ENPP1 ) Lys121Gln polymorphism predisposes women to PCOS and that these polymorphisms also affect anthropometric variables, glucose metabolism and androgen synthesis. To test those ideas, we studied the genotypes, indexes of insulin resistance, and hormone profiles in 123 Japanese women with PCOS and 380 healthy Japanese controls. We found that there were significantly more IRS-1 972Arg carriers among the PCOS patients than among the healthy controls (10.6% vs. 4.8%, p  = 0.029), which is consistent with our finding that women carrying the IRS-1 972Arg allele had a significantly increased risk of developing PCOS (odds ratio: 3.31, 95% confidence interval: 1.49–7.35). By contrast, the ENPP1 Lys121Arg polymorphism was distributed equally among PCOS patients and controls. In addition, neither of these polymorphisms studied affected the anthropometric variables, metabolic parameters or androgen levels of women with PCOS. We conclude that the IRS-1 Gly972Arg polymorphism is associated with PCOS in the Japanese population.