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Abstract
Aim. This study was designed to examine the relationship between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene and insulin resistance (IR) in first-degree relatives of subjects with polycystic ovary syndrome (PCOS).
Materials and methods. One hundred and twenty family members of 55 patients with PCOS and 80 unrelated healthy control subjects without a family history of diabetes or PCOS were studied. IR was assessed by homeostatic model assessment (HOMA-IR) and area under the curve (AUC) for insulin during an oral glucose tolerance test in subjects with normal glucose tolerance and controls. Genetic analysis of the PPAR-γ gene Pro12Ala polymorphism was performed by restriction fragment length polymorphism.
Results. Fasting insulin, HOMA-IR and AUC insulin were significantly higher in first-degree relatives of PCOS subjects than in controls. A significantly different allele distribution of the Pro12Ala polymorphism of PPAR-γ was observed between the two groups, with the frequency of the variant Ala isoform being significantly reduced in the first-degree relatives of PCOS subjects (10.8%, 13 subjects) compared with the control group (22.5%, 18 subjects). All Pro12Ala polymorphisms of the PPAR-γ gene were heterozygous. Compared with first-degree relatives of PCOS subjects with the Pro12Pro polymorphism of PPAR-γ, first-degree relatives of PCOS subjects with the Pro12Ala polymorphism had low fasting insulin, HOMA-IR and AUC insulin levels. The combined prevalence rate for impaired glucose tolerance, impaired fasting glucose and diabetes was 40% (16 subjects) in mothers and 52% (20 subjects) in fathers of PCOS women.
Conclusion. Our findings suggest that Pro12Ala PPAR-γ gene polymorphism may be protective against IR and might prevent the development of diabetes mellitus in the first-degree relatives of subjects with PCOS.