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DOI: 10.1055/s-2004-819118
The G protein αs subunit T393C polymorphism predicts improvement in insulin sensitivity and weight loss in metformin-treated PCOS-women
Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder characterized by chronic anovulation and hyperandrogenism. Most of the PCOS women also have insulin resistance, putting them at an increased risk to develop a metabolic syndrome. The treatment of insulin resistance in PCOS patients with metformin improves androgen levels and may facilitate weight loss. The G protein αs subunit gene (GNAS1) is known to be involved in the pathogenesis of several endocrine and metabolic disorders (e.g. Cushing’s syndrome, hypertension). To determine its role in PCOS, especially its interaction with the parameters of the metabolic syndrome, 111 PCOS women were genotyped for the common T393C polymorphism in GNAS1. To this end, genomic DNA was amplified by PCR with specific oligonucleotides and genotypes were determined using the restriction enzyme Fok-I. In addition, metabolic parameters were measured in PCOS women before and after 6 months of therapy with metformin. GNAS1 genotype distributions were in Hardy-Weinberg equilibrium and not significantly different between PCOS women and a control group of 195 Caucasian blood donors from the university hospital of Essen. Genotype distribution in PCOS women and controls for CC was 26.1 vs. 25.1%, TC 55 vs. 49.8% and 18.9 vs. 25.1% for TT. Subgroup analysis of 49 PCOS patients who finished the treatment period revealed a genotype-dependent reduction in insulin resistance evidenced by a lower HOMA-IR without significantly different values at baseline. After 6 months HOMA-IR was significantly reduced in CC- (4.8±3.5 to 2.4±1.4, p=0.029) and in TC-subjects (4.6±4.1 to 2.5±2.3, p=0.028) but not in the TT-group. Metformin therapy also induced a 5% reduction of BMI in C-allele carriers (CC: 33±7.8 to 31.4±7.6; TC: 29±7.8 to 27.5±7.2kg/m2) without reducing BMI in TT-genotype (29±7.8 to 29.3±7.8). In conclusion, metformin treatment of PCOS patients was more effective in reducing insulin resistance and BMI in GNAS1-C than in GNAS1-T allele carriers