Association of the Pro 12 Ala polymorphism in peroxisome proliferator - 1 activated receptor 2 ( PPARgamma 2 ) with decreased Basic Metabolic Rate 2 ( BMR ) in women

26 27 Objective: The peroxisome proliferator-activated receptor (PPAR)gamma is a 28 transcription factor involved in glucose homeostasis and energy metabolism. 29 A missense mutation at codon 12 in the PPARgamma2 has been associated 30 with increased body mass index and attenuated Insulin Resistance (IR) in 31 PCOS. We have recently shown a decreased Basic Metabolic Rate (BMR) in 32 PCOS. The aim of the present study was to determine the prevalence of the 33 polymorphism Pro12Ala of the PPAR gamma2 gene and its associations with 34 indices of IR, and BMR in lean and slightly overweight PCOS women. 35 Design: Case-control association study involving 156 PCOS women with 36 biochemical hyperandrogenism and chronic anovulation and polycystic 37 ovarian morphology on ultrasound and 56 unrelated healthy controls. 38 Methods: Hormonal determinations were performed by 39 electrochemiluminescence quantitation or RIA. BMR was measured by 40 indirect calorimetry. All subjects were genotyped by a PCR – RLFP assay. 41 Results: Genotype frequencies of the Pro12Ala polymorphism in 42 (PPAR)gamma2 did not differ among PCOS women and control subjects. 43 The presence of Pro12Ala polymorphism of PPARgamma2 was associated 44 with lower BMR (p =0.04). This finding was valid in our subgroup of lean 45 PCOS (BMI <25 Kg/m), in which the Ala variant was also associated with 46 higher total testosterone values. 47 Conclusion: The Pro12Ala polymorphism in the (PPAR)gamma2 gene is 48 associated with decreased Basic Metabolic Rate (BMR) in women with 49 polycystic ovary syndrome (PCOS) and biochemical hypeandrogenemia. 50 Page 2 of 26