Endocrine Abstracts

Background: Insulin resistance (IR) is the common denominator of three multigenic disorders: type 2 diabetes mellitus, obesity, and PCOS. IR can result from genetic abnormalities involving proteins of the insulin signalling pathway, including PC-1 and IRS-1. The IRS-1 G972R variant had the highest world frequency and correlated with IR in PCOS Sicilian women (Horm Metab Res, 2010).

Objective and methods: To determine: i) the rates of the G972R IRS-1 and K121Q PC-1 polymorphisms in Sicilian PCOS women (n=100) and age-matched controls (n=45); ii) the association of the polymorphisms with the clinical/biochemical phenotypes of PCOS.

Results: The rate of the IRS-1 G972R polymorphism in PCOS and controls was 50 and 24.4% (P=0.004), while the rate of the PC-1 K121Q was 20 and 13.3% (P=0.33). Carriers were always heterozygous (Het), except four PCOS women (two IRS-1 homozygous (Hom), and another two PC-1 Hom). Distribution of genotypes (wild type (WT) or Het-Hom) in PCOS vs controls was: IRS-1/PC-1 WT/WT (44 vs 68.9%, P=0.0055), IRS-1/PC-1 Het-Hom/Het-Hom (14 vs 6.7%, P=0.20), IRS-1 Het-Hom/PC-1 WT (36 vs 17.8%, P=0.027) and IRS-1 WT /PC-1 Het-Hom (6 vs 6.7%, P=0.88). The IRS-1 Het-Hom/PC-1 WT PCOS women had: i) the worst metabolic profile (fasting insulin, HOMA-IR and triglycerides, significant vs IRS-1 WT/PC-1 Het-Hom and IRS-1/PC-1 WT/WT; lower Matsuda index, significant vs IRS-1/PC-1 WT/WT); ii) the worst hormone profile (higher total testosterone and lower estradiol, significant vs IRS-1/PC-1 WT/WT; lower FSH, significant vs IRS-1 WT/PC-1 Het-Hom and IRS-1/ PC-1 Het-Hom/Het-Hom); iii) the youngest age and the lowest hirsutism index (both significant vs IRS-1/PC-1 WT/WT).

Conclusion: Only the G972R IRS-1 polymorphism is significantly more frequent in PCOS women. When this variant is not associated with the K121Q PC-1 variant, the metabolic profile and testosteronemia are worse and age at presentation is anticipated. However, the modest hirsutism suggests relative androgen resistance.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.