Association of Gly972Arg variant of insulin receptor subtrate-1 and Gly1057Asp variant of insulin receptor subtrate-2 with polycystic ovary syndrome in the Chinese population

OBJECTIVE Polycystic ovary syndrome (PCOS) is a common endocrinologic disease in women. In the present study, we examined the relationship of the IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms to PCOS and phenotypic features of PCOS in a Chinese population from Taiwan. MATERIALS AND METHODS A total of three hundred and forty genetically unrelated women with age from 18 to 45 years, including two hundred and forty-eight PCOS patients and ninety-two control subjects, were recruited. The hormone and biochemical measurements were evaluated for each woman. Genotyping of the IRS-1 gene Gly972Arg variant and IRS-2 gene Gly1057Asp variant were performed by using direct sequencing. RESULTS We found significant difference in the genotypic distribution of IRS-2 gene Gly1057Asp between the PCOS group and the control group (p = 0.004). The carriers of homozygous IRS-2 Asp had an increased risk of PCOS compared with the carriers of Gly/Gly (OR 4.08, 95% C.I. 1.60-10.41, p = 0.003). No significant difference in genotype frequencies of IRS-1 Gly972Arg was observed between two groups. We further investigated the effect of interaction of IRS-1 Gly972Arg and IRS-2 Gly1057Asp on the risk of PCOS and found that women carried IRS-1 Gly/Arg or IRS-2 Asp/Asp or carried both IRS-1 Gly/Arg and IRS-2 Asp/Asp had a much higher risk of PCOS compared with their counterpart, respectively (OR 2.49, 95% C.I. 1.16-5.37, p = 0.019; OR 11.87, 95% C.I. 1.21-116.84, p = 0.034). We further found, the non-obese PCOS patients carried significantly higher frequency of IRS-2 Asp/Asp as compared with the control group (p = 0.004). A significant effect of interaction of carrying both IRS-1 Gly/Arg and IRS-2 Asp/Asp was also observed in the non-obese PCOS patients (p = 0.003), but not in the obese PCOS patients. CONCLUSIONS In this study, we found significant association of the variant of IRS-2 gene as well as the interaction of IRS-1 and IRS-2 genes with PCOS, especially in non-obese women. Women with IRS-2 homozygous Asp variant may be considered as a risk factor for PCOS that needs early detection to prevent further complication in the Chinese population from Taiwan.