Prevalence of CYP21 Mutations and IRS1 Variant Among Women With Polycystic Ovary Syndrome and Adrenal Androgen Excess

The study examined 114 women with polycystic ovary syndrome (PCOS) and 95 healthy controls to assess the frequency of CYP21 gene mutations and the G972R variant of the IRS1 gene, particularly in the context of adrenal androgen (AA) excess. It was found that 14.7% of PCOS patients carried CYP21 mutations and 13.8% carried the IRS1 variant. Among PCOS patients with AA excess, 18.5% had CYP21 mutations, and the frequency of combined heterozygosity for CYP21 and IRS1 variants was significantly higher in women with PCOS and AA excess compared to other groups (P=.046). Despite this, there were no significant differences in allele frequency between PCOS patients with and without AA excess and controls, suggesting that these genetic factors have a limited role in the development of PCOS. The study suggests that while the IRS1 variant may act as a modifier locus among women with CYP21 mutations, increasing the risk of AA excess, overall, these genetic factors are not major contributors to PCOS in the studied population.