Evidence for association of polycystic ovary syndrome in Caucasian women with a marker at the insulin receptor gene locus

The polycystic ovary syndrome (PCOS) is one of the commonest female endocri nopathies affecting 5-10% of women of reproductive age. The disorder, chara cterized by chronic anovulation and signs of hyperandrogenism, results from a complex interaction between genetic predisposing factors and environment al triggers. We have studied 85 Caucasian PCOS patients and 87 age-matched Caucasian control women for associations with four candidate genes: follist atin, CYP19 (aromatase), CYP17a, and the insulin receptor (INSR). These gen es were analyzed using microsatellite markers located near or inside the ge nes. We found that only the insulin receptor gene marker D19S884 was signif icantly associated with PCOS (p=0.006 and even after a conservative correct ion p=0.042). The INSR gene region was then fine mapped with an additional panel of 9 markers but only marker D19S884, located 1 cM telomeric to the I NSR gene, was again associated with PCOS. In conclusion, our results sugges ted that a susceptibility gene for PCOS was located on chromosome 19p13.3 i n the insulin receptor gene region. It remains to be determined if this sus ceptibility gene is the insulin receptor gene itself or a closely located g ene. Since insulin stimulates androgen secretion by the ovarian stroma it i s likely that INSR function in the ovary is involved in the genetic suscept ibility to PCOS.