期刊
GENES AND IMMUNITY
卷 21, 期 1, 页码 63-70出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41435-019-0082-z
关键词
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资金
- Medical Research Council [G1100449]
- European Society of Clinical Microbiology & Infectious Diseases (Research Grant 2013)
- National Institute for Health Research [ACF2016-20-001]
- Wellcome Trust Investigator Award [204969/Z/16/Z]
- European Union [279185]
- National Institute for Health Research Oxford Biomedical Research Centre, Oxford, UK
- Wellcome Trust Core Awards [090532/Z/09/Z, 203141/Z/16/Z]
- Health Data Research UK
- National Institute for Health Research Oxford Biomedical Research Centre
- Wellcome Trust [203141/Z/16/Z]
- National Institute for Health Research Imperial Biomedical Research Centre, London, UK
- National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, London, UK
- MRC [G1100449] Funding Source: UKRI
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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