Genetic Determinants of Insulin Action in Polycystic Ovary Syndrome

Abstract

Introduction: Insulin resistance is associated with both type 2 diabetes (T2 D) and polycystic ovary syndrome (PCOS). There is an association of T2 D with several polymorphisms in candidate genes related to insulin resistance. However, there is limited information about the association of these polymorphisms with PCOS. Methods: 57 non-diabetic women with PCOS and a control group of 567 healthy non-diabetic women underwent an oral glucose tolerance test (OGTT). They were genotyped for the polymorphisms Gly972Arg in IRS-1, Gly1057Asp in IRS-2, SNP 43, 44, and 45 in CAPN10, Pro12Ala in PPARγ2, C-512 T in FOXC2, and T45 G in adiponectin. Results: Women with PCOS had higher 2-h blood glucose levels (6.5 ± 0.2 vs. 6.0 ± 0.06 mmol/l, p = 0.03) compared to control women, higher fasting insulin (79 ± 7 vs. 53 ± 2 pmol/l, p = 0.02), and a lower insulin sensitivity estimated from the OGTT (12.4 ± 1.1 vs. 19.1 ± 0.5 U, p = 0.0001). More homozygous G allele carriers of the T45 G polymorphism in the adiponectin gene were found in women with PCOS compared to controls (13.2 % vs. 2.6 %, p = 0.008). In women with PCOS, G-allele carriers had lower fasting insulin levels than TT carriers (61 ± 9 vs. 88 ± 10, p = 0.02) in contrast to controls (p = 0.03 for interaction genotype × PCOS). The other polymorphisms were distributed equally among women with PCOS and controls (all p > 0.5). Summary: We found a higher prevalence of the T45 G polymorphism in the adiponectin gene in women with PCOS compared to controls. This was not associated with a more insulin resistant phenotype in PCOS, however. Other frequent polymorphisms in genes related to insulin resistance and type 2 diabetes showed no association with PCOS.

Key words

Polycystic ovary syndrome - polymorphism - insulin resistance - linkage - genetics

References

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