Association of the Pro12Ala polymorphism in peroxisome proliferator-activated receptor γ2 with decreased basic metabolic rate in women with polycystic ovary syndrome

Objective: The peroxisome proliferator-activated receptor (PTAR)gamma is a transcription Factor involved in glucose homeostasis and energy metabolism. A missense mutation at codon 12 in the PPAR gamma 2 has been associated with increased body mass index (BMI) and attenuated insulin resistance (IR) in polycystic ovary syndrome (PCOS). We have recently shown it decreased basic metabolic rate (BMR) ill PCOS. The aim Of the Present study is to determine the prevalence of the Pro12Ala polymorphism of the PPAR gamma 2 gene and its associations with indices of IR and BMR ill lean and slightly overweight PCOS women. Design: Case-control association study involving 156 PCOS women with biochemical hyperandrogenism, chronic anovulation and polycystic ovarian morphology in ultrasound and 56 unrelated healthy controls. Methods: Hormonal determinations were performed by electrochemiluninescence quantitation or RIA BMR was measured by indirect calorimetry All Subjects were genotyped by a PCR-restriction fragment length polymorphism assay. Results: Genotype frequencies of the Pro12Ala polymorphism in PPAR gamma 2 did not: differ among PCOS women and control subjects. The presence of Pro12Ala polymorphism of PPAR gamma 2 was associated with lower BMR (P=0.04). This finding was valid in Our Subgroup of lean PCOS (BMI < 2 5 kg/m(2)). ill which the Ala variant was also associated with higher total testosterone values. Conclusion: The Pro12Ala polymorphism in the PPAR gamma 2 gene is associated with decreased BMR in women with PCOS and biochemical hyper-androgenemia. These young women are therefore at risk to increase their body weight and should restrict their energy intake by diet and enhance their energy expenditure by exercise.