Association of SLC11A1 promoter polymorphisms with the incidence of autoimmune and inflammatory diseases: a meta-analysis.

Solute carrier family 11 member a1 (SLC11A1) exerts pleiotropic effects on macrophage function. Expression of SLC11A1 is regulated by a (GT)(n) microsatellite promoter repeat polymorphism of which nine alleles have been described. Enhanced activation of macrophages, associated with increased expression from allele 3, may be functionally linked to the development of autoimmune and inflammatory diseases. Conversely, low expression, driven by allele 2, may afford resistance. We have performed a meta-analysis to determine the association of SLC11A1 promoter alleles 2 and 3 with autoimmunity and inflammation. A random effects pooled odds ratio (OR) of 1.04 (95% confidence interval [CI]=0.20) for allele 3 suggested a weak association of this allele with an increased risk of disease. Calculation of the OR in the absence of asymmetry yielded a random effects pooled OR of 0.88 (95% CI=0.66), effectively reversing the above association. A fixed effects pooled OR of 0.90 (95% CI=0.24) was obtained for allele 2, suggesting a weak predominance of disease in the absence of this allele. Application of the trim-and-fill method resulted in a fixed effects OR of 0.80 (95% CI=0.22), thus strengthening this association. Associations of allele 3 with autoimmune and inflammatory diseases reported in several association studies may be attributable to some form of bias amongst published results.