Meta-analysis of TNF-α promoter-308 A/G polymorphism and SLE susceptibility

Alleles of tumor necrosis factor-alpha (TNF-alpha) gene have been inconsistently associated with systemic lupus erythematosus (SLE), particularly the 308-A/G functional promoter polymorphism. To generate large-scale evidence on whether 308-A/G promoter polymorphism is associated with SLE susceptibility we have conducted a meta-analysis. We have identified 21 studies of this polymorphism and SLE using MEDLINE search. Meta-analysis was performed for genotypes A/A (recessive effect), A/A+A/G (dominant effect), and A allele in fixed or random effects models. All control samples were in Hardy-Weinberg proportion. The overall odds ratio ( OR) of the A/A genotype was 3.2 (95% CI = 2.0-5.3, P < 0.001). Stratification by ethnicity indicated that the A/A genotype was associated with SLE in European-derived population (OR 4.0, CI = 2.5-6.4, P < 0.001). No association was detected in Asian-derived population (OR, 1.3, CI = 0.3-6.3, P = 0.76). The overall OR for the risk genotypes (A/A and A/G) was 2.0 (CI = 1.3-3.1, P < 0.001). Similar results were found between the risk allele A and SLE where a significant association was found in European population (OR = 2.1, CI = 1.6-2.7, P < 0.001), but not in Asian (OR = 1.4, CI = 0.8-2.3, P = 0.2) or African (OR = 1.2, CI = 0.6-2.5, P = 0.59) populations. In summary, this meta-analysis demonstrates that the TNF-alpha promoter -308 A/G polymorphism may confer susceptibility to SLE, especially in European-derived population.