Invasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1540 controls. Using HLA imputation and linear mixed models, we find each copy of the HLA-DQA1*01:03 allele associates with a twofold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4, P = 0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.
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Adult, Case-Control Studies, Female, Gene Frequency, Genes, MHC Class II, Genetic Predisposition to Disease, HLA Antigens, HLA-DQ alpha-Chains, Haplotypes, Histocompatibility Antigens Class I, Humans, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Risk Factors, Streptococcal Infections, Streptococcus pyogenes