Objective: Although many case-control studies have investigated the association between the SLC11 A1 gene polymorphisms and tuberculosis (TB) susceptibility, results were conflicting due to limited power. We reviewed the literature systematically by means of meta-analysis, provided a quantitative summary estimate on the association with TB, and examined some sources of between-study heterogeneity.
Design: We searched databases (MEDLINE, PUBMED and OVID) from January 1995 to December 2004 using 'gene' or 'SLC11A1' or 'NRAMP1', in combination with 'tuberculosis', performed a manual search of citations from relevant original studies and review articles, or corresponded with authors.
Results: The summary ORs for studies with 3'UTR, D543N, INT4 and 5'(GT)n loci allele variants in the SLC11A1 gene were 1.33 (95%CI 1.08-1.63), 1.67 (95%CI 1.36-2.05), 1.14 (95%CI 0.96-1.35) and 1.32 (95%CI 1.03-1.68), respectively, compared with their corresponding common alleles. The pooled ORs by sub-group analyses for the four loci described above were 1.20 (95%CI 0.86-1.68), 1.69 (95%CI 1.14-2.50), 1.50 (95%CI 1.17-1.91), and 1.31 (95%CI 1.05-1.64) in subjects of African descent, 1.46 (95%CI 1.10-1.94), 1.65 (95%CI 1.29-2.12), 0.91 (95%CI 0.66-1.25) and 1.86 (95%CI 1.33-2.62) in Asian subjects, 1.81 (95%CI 0.66-4.93), 1.79 (95%CI 0.72-4.47), 0.87 (95%CI 0.61-1.22) and 1.02 (95%CI 0.35-2.99) in European subjects.
Conclusions: Polymorphisms at the four loci had no statistically significant association between the SLC11A1 variants and susceptibility to TB in subjects of European descent, while they showed a statistically significant association in Asian subjects (except the INT4 variant), African subjects (except the 3'UTR variant) and the population as a whole (except the INT4 variant).