OBJECTIVE: Insulin receptor substrate (IRS) proteins are critical to signal transduction in insulin target tissues. The present study was undertaken to determine whether IRS-1 Gly972Arg and IRS-2 Gly1057Asp influence hormonal and metabolic characteristics in Greek patients with polycystic ovary syndrome (PCOS) and controls.MATERIAL AND METHODS: One hundred and eighty-three women with PCOS and 88 healthy volunteers were enrolled. Venous blood samples were obtained for genetic study and hormonal profile, glucose, and insulin assays, on days 3 to 7 from cycling patients. DNA was extracted by whole blood samples for genotyping and detection of IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms.RESULTS: Fifty-six women with PCOS (30.60%), whereas 12 women in the control group (13.64%) carried the IRS-1 polymorphism (p = 0.0026). No statistically significant differences in genotypes or allele frequencies for IRS-2 polymorphism were observed between controls and PCOS women. No significant differences in any clinical or hormonal measures between subjects on the basis of genotype were observed, except the increased levels of fasting glucose that exhibit the carriers of the Asp allele of the IRS-2 polymorphism.CONCLUSIONS: Only the IRS-1 polymorphism is associated with increased susceptibility to PCOS in a Greek population. These loci should not be considered as major contributors to the hormonal and metabolic phenotype of PCOS.