Association between Pro12Ala polymorphism of the PPAR-gamma2 gene and insulin sensitivity in Brazilian patients with type-2 diabetes mellitus.

摘要

Aim: Peroxisome-proliferator-activated receptor-gamma2 (PPAR-gamma2) is a nuclear receptor that plays an important role in lipid metabolism and insulin sensitivity. The purpose of this study is to investigate the association of Pro12Ala polymorphism at the PPAR-gamma2 gene in Brazilian patients with type-2 diabetes mellitus (T2Dm) and controls (CG). Methods: Genomic DNA was obtained from 207 unrelated white people presenting with T2Dm and from 170 controls. Anthropometric data included body mass index and waist to hip ratio. Biochemical parameters included fasting plasma glucose, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, glycated haemoglobin and insulin. Systolic and diastolic blood pressures were also measured. Screening for mutations in the entire coding region of the PPAR-gamma gene was performed by means of polymerase chain reaction (PCR), single-strand conformational polymorphism and sequencing. Pro12Ala polymorphism was analysed by using PCR-RFLP (restriction fragment-length polymorphism). Results: One base substitution was identified - a C to G substitution in exon B of the PPAR-gamma2 gene. The frequency of the Ala12 allele in T2Dm (0.09) was similar to that found in CG (0.06, p = 0.185). In the T2Dm group, Ala12 allele was associated with lower fasting plasma insulin levels (p = 0.036) and higher insulin sensitivity (p = 0.049) by means of homeostasis model assessment. Among obese people, there was no association between any of the T2Dm or obesity-related traits and the Pro12Ala polymorphism. Conclusions: The results of our study suggest that people with the Ala12 allele of the PPAR-gamma2 gene could be more sensitive to insulin than those carriers of the Pro12 allele among Brazilian Caucasians.