Host genetic variants near the PAX5 gene locus associate with susceptibility to invasive group A streptococcal disease
Parks T., Auckland K., Lamagni T., Mentzer A., Elliott K., Guy R., Cartledge D., Strakova L., O'Connor D., Pollard A., Chapman S., Thomas M., Brodlie M., Colot J., D'Ortenzio E., Baroux N., Mirabel M., Gilchrist J., Scott A., Williams T., Knight J., Steer A., Hill A., Sriskandan S.
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.