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- Title
PPARγ2 Pro12A1a and TNFα-308 G/A Interaction on Features of Metabolic Syndrome.
- Authors
Gonzalez-Sanchez, Jose L.; Zabena, Carina; Martínez-Larrad, Maria T.; Martínez-Calatrava, Maria J.; Perez-Barba, Milagros; Serrano-Ríos, Manuel
- Abstract
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.
- Publication
Diabetes, 2007, Vol 56, pA304
- ISSN
0012-1797
- Publication type
Academic Journal