A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus.

Willcocks, Lisa C., Carr, Edward J., Niederer, Heather A., Rayner, Tim F., Williams, Thomas N., Yang, Wanling, Scott, J. Anthony G., Urban, Britta ORCID: https://orcid.org/0000-0002-4197-8393, Peshu, Norbert, Vyse, Timothy J., Lau, Yu Lung, Lyons, Paul A. and Smith, Kenneth G. C. (2010) 'A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus.'. Proceedings of the National Academy of Sciences of the United States of America, Vol 107, Issue 17, pp. 7881-7885.

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Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease more prevalent in people of African and Asian origin than Caucasian origin. FcgammaRIIb is an inhibitory Fc receptor with a critical role in immune regulation. Mouse data suggest that FcgammaRIIb 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.

Item Type:	Article
Uncontrolled Keywords:	genetic association study; autoimmunity; infectious disease; selection; bacterial septicaemia
Subjects:	QW Microbiology and Immunology > Immunity by Type > QW 545 Autoimmunity WC Communicable Diseases > WC 20 Research (General) WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 240 Bacteremia. Sepsis. Toxemias WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department:	Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI):	https://doi.org/10.1073/pnas.0915133107
Depositing User:	Mary Creegan
Date Deposited:	09 Jul 2010 11:04
Last Modified:	06 Feb 2018 13:00
URI:	https://archive.lstmed.ac.uk/id/eprint/1033

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