Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 17, Pages 7881-7885Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0915133107
Keywords
genetic association study; autoimmunity; infectious disease; selection; bacterial septicaemia
Categories
Funding
- Wellcome Trust [083650/Z/07/Z, 077092, 079895, 076934, 081835, 079082]
- National Institute for Health Research Cambridge Biomedical Research Centre
- BioMalpar Network 6 Network of Excellence
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Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease more prevalent in people of African and Asian origin than Caucasian origin. Fc gamma RIIb is an inhibitory Fc receptor with a critical role in immune regulation. Mouse data suggest that Fc gamma RIIb deficiency increases susceptibility to autoimmune disease but protects against infection. We show that a SNP in human FCGR2B that abrogates receptor function is strongly associated with susceptibility to SLE in both Caucasians and Southeast Asians. The minor allele of this SNP is more common in Southeast Asians and Africans, populations from areas where malaria is endemic, than in Caucasians. We show that homozygosity for the minor allele is associated with substantial protection against severe malaria in an East African population (odds ratio = 0.56; P = 7.1 x 10(-5)). This protective effect against malaria may contribute to the higher frequency of this SNP and hence, SLE in Africans and Southeast Asians.
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