Meta-analysis on the G-308A tumor necrosis factor α gene variant and phenotypes associated with the metabolic syndrome

Objective: The G-308A tumor necrosis factor (TNF) alpha gene variant has been associated with obesity, insulin resistance, and hypertension. We performed a systematical review of the literature by means of a meta-analysis to assess the association of the G-308A TNF alpha polymorphism with the components of the metabolic syndrome. Research Methods and Procedures: Studies were identified by searches of the literature for reports using the terms: diabetes, insulin resistance, hypertension, obesity or metabolic syndrome and TNF, variants or polymorphism or alleles, and Nco or -308. From 824 reports, we included 31 observational studies, case control and cohort at baseline, which analyzed the association between the TNF alpha polymorphism and one or more components of the metabolic syndrome. A fixed effect model was used to pool data from individual studies. Results: Obesity [odds ratio, 1.23; 95% confidence interval (CI), 1.045 to 1.45; p=0.013] in a total of 3562 individuals from eight homogeneous studies, systolic arterial blood pressure (standardized difference, 0.132; 95% CI, 0.016 to 0.25; p<0.03) in a total of 1624 individuals from four homogeneous studies and plasma insulin levels (standardized difference, 0.095; 95% CI, 0.020 to 0.17; p=0.013) in a total of 3720 subjects from 16 homogeneous studies were positively associated with the -308A variant. Discussion: These results indicate that individuals who carried the -308A TNF alpha gene variant are at 23% risk of developing obesity compared with controls and showed significantly higher systolic arterial blood pressure and plasma insulin levels, supporting the hypothesis that the TNF alpha gene is involved in the pathogenesis of the metabolic syndrome.