Effect of the Pro12Ala polymorphism of the PPAR gamma 2 gene on response to pioglitazone treatment in menopausal women.Menopause. 2008 Nov-Dec; 15(6):1151-6.M
To investigate the influence of the Pro12Ala polymorphism of the PPAR gamma 2 gene on metabolic and hormonal response to pioglitazone treatment in obese postmenopausal women.
We included 102 obese (body mass index [BMI] >or=30 kg/m2) and 97 nonobese (BMI <or=27 kg/m2) postmenopausal women. Anthropometric data were collected, and fasting glucose, insulin, leptin, follicle-stimulating hormone, luteinizing hormone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, testosterone, estrone, estradiol, and adiponectin were measured and the PPAR gamma 2 Pro12Ala genotypes were determined. Eighty-three obese postmenopausal women were treated with pioglitazone 15 mg/day for 15 days, and hormone levels and insulin resistance (homeostasis model assessment of insulin resistance) were assessed before and after treatment.
Obese women had a higher BMI, waist-to-hip ratio, fasting glucose, insulin, homeostasis model assessment of insulin resistance, leptin, dehydroepiandrosterone, estradiol, testosterone, and adiponectin levels, whereas the follicle-stimulating hormone level was lower. Genotype frequencies were similar in obese and nonobese women. Analysis of the whole group showed that women with the Pro/Ala genotype had a higher BMI, waist-to-hip ratio, and fasting glucose (P < 0.04, P < 0.02, and P < 0.004, respectively) than the group with the Pro/Pro genotype. After pioglitazone treatment, glucose levels decreased in both genotypes, but at a greater amount in carriers of the Pro/Ala genotype (-15 mg/dL vs -7 mg/dL, P < 0.003). However, insulin and homeostasis model assessment of insulin resistance levels were lower in carriers of the Pro/Pro genotype (-4.0 vs 0.7 IU/L, P=0.009 and -1.0 vs -0.08, P = 0.03, respectively).
The Pro/Ala genotype of PPAR gamma 2 was associated with obesity and higher fasting glucose. Pioglitazone treatment in obese women with the Pro/Ala genotype induced a greater glucose decrease, and obese women may derive more benefit from this drug.