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Genetic variants of SLC11A1 are associated with both autoimmune and infectious diseases: systematic review and meta-analysis

Genes & Immunity volume 16, pages 275–283 (2015)Cite this article

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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.

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Acknowledgements

We thank Jenefer M Blackwell, Anna Dubaniewicz, AM Graham, Leonardo A Sechi, Lee E Sieswerda, Maria Gazouli, Margje Haverkamp, Linda Wicker, Jennie Yang, Eileen Hoal, Timothy Sterling and Alison Motsinger-Reif for supplying the additional population data. NSA was funded through an Australian Postgraduate Award.

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  1. School of Medical and Molecular Biosciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia

    N S Archer, N T Nassif & B A O'Brien

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Archer, N., Nassif, N. & O'Brien, B. Genetic variants of SLC11A1 are associated with both autoimmune and infectious diseases: systematic review and meta-analysis. Genes Immun 16, 275–283 (2015). https://doi.org/10.1038/gene.2015.8

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