RS1799817 in INSR associates with susceptibility to polycystic ovary syndrome

BACKGROUND: Insulin and its receptor (INSR) have been implicated in the etiology of the polycystic ovarian syndrome (PCOS). Here, we investigate the association between INSR rs1799817 polymorphism and PCOS in Saudi Arabian women. METHODS: Study group included 126 PCOS women and 118 normo-ovulatory matched controls. The demographic data was recorded, and the plasma levels of glucose, lipids, leptin, E2, LH, FSH, T, SHBG, and insulin were determined. The genotypic and allele frequencies of rs1799817 were evaluated in both PCOS and control group. Polymerase chain reaction (PCR) was used to amplify Exon 17 of the INSR gene, and the amplified products were analyzed by direct sequencing. A single-nucleotide polymorphism (C to T) was found at locus 10923 (His1058) of rs1799817. RESULTS: In the PCOS group, the mutant allele T occurs at a significantly higher frequency (0.306) compared to the control group (0.174) (p<0.001). It shows a dominant effect and elevates the relative risk of PCOS even in the heterozygotes (RR=2.82). After stratification of the participants by body mass index, the frequency of T allele was significantly higher in the lean patients with PCOS compared to the lean control. The obese PCOS also had a higher frequency than the obese control, but the difference was not statistically significant. Several parameter values were affected by the INSR genotype, particularly W/H ratio, lipid, insulin and glucose levels and insulin resistance in PCOS patients. CONCLUSIONS: The INSR gene polymorphism rs1799817 is a susceptibility locus associated with PCOS in Saudis and associated metabolic and hormonal changes, particularly, in the lean PCOS females.