Association of Inflammation Genes with Alcohol Dependence/Abuse: A Systematic Review and a Meta-Analysis

Abstract

The aim of the present work was to systematically review all association studies of inflammation genes with alcohol dependence/alcohol abuse (AD/AA) and to perform a meta-analysis. Odds ratios (ORs) were estimated by contrasting the ratio of counts of the ‘high-risk’ versus ‘low-risk’ alleles in AD/AA cases versus controls. Data reported in at least three published studies were available for four genetic polymorphisms [TNF-α -238 (rs361525, G/A); TNF-α -308 (rs1800629, G/A); IL-1RA (VNTR [86 bp]_n); IL-10 -592 (rs1800896, C/A)]. In total, nine meta-analyses were performed. Of these, only the TNF-α -238 polymorphism showed a significant association with AD/AA (OR = 1.36, 95% CI: 1.05–1.76). This risk remained significant and increased slightly when we considered only patients with advanced alcohol-related liver disease (AALD) (OR = 1.5, 95% CI: 1.13–1.98) but not when we considered only patients without AALD (OR = 1.08, 95% CI: 0.5–2.35). Sensitivity analysis showed that this genetic association is derived from the AALD phenotype rather than from AD. Our approach is limited by our phenotype definition; some studies included chronic heavy drinkers (minimal daily consumption of 80 g for a minimal duration of 10 years) but without a standardized psychiatric assessment.