Tumor necrosis factor alpha -308G>A, -863C>A, -857C>T gene polymorphisms and tuberculosis susceptibility: a meta-analysis.

A large number of studies have shown that polymorphisms in the tumor necrosis factor-α (TNF-α, TNFA) gene are implicated in susceptibility to tuberculosis (TB). However, the results are inconsistent. We performed this meta-analysis to estimate the association between polymorphisms in the TNFA gene and TB susceptibility.Relevant studies published before March 2012 were identified by searching PubMed, ISI web of knowledge, EBSCO and CNKI. The strength of relationship between the TNFA gene and TB susceptibility was assessed using odds ratios (ORs).A total number of twenty-three case-control studies including 3630 cases and 4055 controls were identified referring to three previously chosen single-nucleotide polymorphisms (SNPs): -308G>A, -863C>A and -857C>T. No association was found between -308G>A, -863C>A and TB susceptibility: -308G>A (GG+GA vs. AA): OR 0.85, 95%CI: 0.55-1.30, P=0.44; -863C>A (CC+CA vs. AA): OR 0.93, 95%CI: 0.84-1.81, P=0.83. Increased risk of TB was associated with -857C>T in the dominant genetic model (CC+CT vs. TT: OR 2.13, 95%CI: 1.25-3.63, P=0.01), the heterozygote comparison (CT vs. TT: OR 2.69, 95%CI: 1.44-5.02, P=0.00) and the homozygote comparison (CC vs. TT: OR 2.08, 95%CI: 1.22-3.53, P=0.01) in Asian subjects.There is an increased association between TNFA -857C>T polymorphism and TB risk among Asian subjects. No association was found between -308G>A and -863C>A with TB risk. Due to several limitations in the present study, well-designed epidemiological studies with large sample size among different ethnicities should be performed in the future.