Effect of the Pro12Ala polymorphism of the PPARγ2 gene on response to pioglitazone treatment in menopausal women

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Abstract

Objective:

To investigate the influence of the Pro12Ala polymorphism of the PPARγ2 gene on metabolic and hormonal response to pioglitazone treatment in obese postmenopausal women.

Design:

We included 102 obese (body mass index [BMI] ≥30 kg/m2) and 97 nonobese (BMI ≤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 PPARγ2 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.

Results:

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).

Conclusions:

The Pro/Ala genotype of PPARγ2 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.

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