PPARγ2 Pro12A1a and TNFα-308 G/A Interaction on Features of Metabolic Syndrome.

To determine whether the Pro12A1a polymorphism of the PPARγ2 gene was associated with increased risk for the development of insulin resistance and other features of the metabolic syndrome in a representative sample of Spanish population and its interaction with the TNF-α-308 G/A polymorphism, we genotyped 783 unrelated subjects recruited from a cross-sectional population-based epidemiological survey in Segovia, Spain (The Segovia Study Group). Anthropometric parameters: BMI, waist to hip ratio (WHR). OGTT, fasting and 2 hrs glucose; serum insulin, adiponectin levels (RIA); lipid profile. Plasma PAI-1 and plasma soluble TNF-αreceptor 2 (sTNFR2) levels by ELISA. Insulin resistance was assessed by HOMA-IR. Categories of glucose tolerance (ADA Clinical Practice Recommendations 2006) MS was defined according to the 2005 IDF criteria. Pro12A1a PPARγand -308G/A TNF-α genotypes determined by PCR-RFLP. PPARγ genotype distribution: Pro12Pro 87.2%, Pro12A1a 12.4%, A1a12A1a: 0.4%. Impaired glucose tolerance (IGT) was higher in Pro 12Pro homozygous compared to carriers of the A1a12 allele (16.8% vs 8.1%, p=027) even after adjustment for sex, age, BMI, WHR and insulin resistance (OR: 2.5, CI 95% 1.04-6.25, p=0.049) in a logistic regression model. Plasma levels of sTNFR2 were positively correlated with BMI, and waist circumference among type 2 diabetic subjects. Interestingly diabetic subjects carrying the -308A allele had higher sTNFR2 levels,. WHR, insulin 2 hours PAI levels,and lower adiponectin concentrations as compared with G-308G homozygous. A gene-gene interaction was detected. Subjects simultaneously having the Ala12 allele of the PPARγ2 gene and the -308A allele of the TNF-α gene had higher waist to hip ratio than those carrying only either one of these gene polymorphisms alone (P<0.001), independently of sex, age, and glucose tolerance status. Our findings indicate a gene-gene interaction between the PPARγPro12Ala polymorphism and the TNF-α-308Apolymorphism, which may result in higher risk for abdominal obesity, but not for type 2 diabetes. [ABSTRACT FROM AUTHOR]