Influence of two polymorphisms of the tumoral necrosis factor-alpha gene on the obesity phenotype.

Several populational-based studies have suggested an association between tumoral necrosis factor-alpha (TNF-alpha) polymorphisms and obesity-related phenotypes. Therefore, this study aimed at assessing the situation (frequency and associated phenotype) of two TNF-alpha common polymorphisms in a Spanish population. In a case-control design study, a group of Spanish subjects (n=313) were genotyped for the TNF-alpha G/A -308 and -238 polymorphisms. Obese subjects (cases) were compared with lean individuals (controls) according to body mass index (BMI; cases: BMI >30 kg/m2, controls: BMI <25 kg/m2). Waist-to-hip ratio, body composition and some metabolic indicators were assessed. The frequency of the -308A allele (0.14) and -238A allele (0.09) was similar to those previously reported in other Caucasian populations. Interestingly, cases with the -308A allele of the TNF-alpha gene have significantly higher hip and waist circumferences (p<0.05), BMI (p<0.01) and body fat mass (p<0.05) values than obese individuals carrying the -308G allele, but not the waist-to-hip ratio. No apparent influence of the -308A polymorphism on other metabolic indicators (insulin and leptin levels) was found. We could not detect any association between the substitution at position -238 polymorphism of the TNF-alpha gene and obesity anthropometrical phenotypes in this Spanish population, despite some differences in plasma leptin. These results support the hypothesis that the G/A -308 polymorphism of the TNF-alpha gene is associated with a higher BMI as well as hip ad waist circumferences, particularly on female bearers, while no influence on such measurements was found for the G/A -238 TNF-alpha gene polymorphism, but only an effect on leptinaemia.