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

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 susceptibili...

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Vydáno v:Proceedings of the National Academy of Sciences - PNAS Ročník 107; číslo 17; s. 7881
Hlavní autoři: Willcocks, Lisa C, Carr, Edward J, Niederer, Heather A, Rayner, Tim F, Williams, Thomas N, Yang, Wanling, Scott, J Anthony G, Urban, Britta C, Peshu, Norbert, Vyse, Timothy J, Lau, Yu Lung, Lyons, Paul A, Smith, Kenneth G C
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 27.04.2010
Témata:
Asian People - genetics
Base Sequence
DNA Primers - genetics
Genetic Predisposition to Disease - genetics
Genome-Wide Association Study
Genotype
Homozygote
Hong Kong
Humans
Lupus Erythematosus, Systemic - genetics
Malaria - genetics
Molecular Sequence Data
Odds Ratio
Polymorphism, Single Nucleotide - genetics
Receptors, IgG - genetics
Sequence Analysis, DNA
United Kingdom
White People - genetics
Hong Kong
United Kingdom
ISSN:1091-6490, 1091-6490
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Popis
Shrnutí: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.
Bibliografie:ObjectType-Article-1
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.0915133107