title: Genetic variants of SLC11A1 are associated with both autoimmune and infectious diseases: systematic review and meta-analysis.
abstract: A systematic review and meta-analyses were undertaken to investigate the association of SLC11A1 genetic variants with disease occurrence. Literature searching indentified 109 publications to include in the meta-analyses assessing the association of 11 SLC11A1 variants with autoimmune and infectious disease. The (GT)n promoter alleles 2 and 3 (rs534448891), which alter SLC11A1 expression, were significantly associated with tuberculosis (OR=1.47 (1.30-1.66), OR=0.76 (0.65-0.89), respectively) and infectious disease (OR=1.25 (1.10-1.42), OR=0.83 (0.74-0.93), respectively). However, although no association was observed with autoimmune disease, a modest significant association was observed with type 1 diabetes (allele 2 OR=0.94 (0.89-0.98)). On the basis of a stronger association of (GT)n allele 2 with tuberculosis, compared with the protective effect of allele 3, we hypothesise that allele 2 is likely the disease-causing variant influencing disease susceptibility. Significant associations were observed between the 469+14G/C polymorphism (rs3731865) and autoimmune disease (OR=1.30 (1.04-1.64)) and rheumatoid arthritis (OR=1.60 (1.20-2.13)) and between the -237C/T polymorphism (rs7573065) and inflammatory bowel disease (OR=0.60 (0.43-0.84)). Further, significant associations were identified between the 469+14G/C, 1730G/A and 1729+55del4 polymorphisms (rs3731865, rs17235409 and rs17235416, respectively) and both infectious disease per se and tuberculosis. These findings show a clear association between variants in the SLC11A1 locus and autoimmune and infectious disease susceptibility.
authors: School of Medical and Molecular Biosciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia.
authors: N S
authors: NS
authors: Archer
authors: School of Medical and Molecular Biosciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia.
authors: N T
authors: NT
authors: Nassif
authors: School of Medical and Molecular Biosciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia.
authors: B A
authors: BA
authors: O'Brien
mesh_terms: D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007239:Infections / Q000453:epidemiology / Q000235:genetics*; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1