Host genetic variants near the PAX5 gene locus associate with susceptibility to invasive group A streptococcal disease
Parks, T.; Auckland, K.; Lamagni, T. L.; Mentzer, A. J.; Elliott, K.; Guy, R.; Cartledge, D.; Strakova, L.; O'Connor, D.; Pollard, A. J.; Chapman, S. J.; Thomas, M.; Brodlie, M.; Colot, J.; D'Ortenzio, E.; Baroux, N.; Mirabel, M.; Gilchrist, J. J.; Scott, J. A. G.; Williams, T. N.; Knight, J. C.; Steer, A. C.; Hill, A. V. S.; Sriskandan, S.
Show abstract
We undertook a genome-wide association study of susceptibility to invasive group A streptococcal (GAS) disease combining data from distinct clinical manifestations and ancestral populations. Amongst other signals, we identified a susceptibility locus located 18kb from PAX5, an essential B-cell gene, which conferred a nearly two-fold increased risk of disease (rs1176842, odds ratio 1.8, 95% confidence intervals 1.5-2.3, P=3.2x10-7). While further studies are needed, this locus could plausibly explain some inter-individual differences in antibody-mediated immunity to GAS, perhaps providing insight into the effects of intravenous immunoglobulin in streptococcal toxic shock.
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