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 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.
Willcocks
Lisa C
LC
Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 0XY, United Kingdom.
Carr
Edward J
EJ
Niederer
Heather A
HA
Rayner
Tim F
TF
Williams
Thomas N
TN
Yang
Wanling
W
Scott
J Anthony G
JA
Urban
Britta C
BC
Peshu
Norbert
N
Vyse
Timothy J
TJ
Lau
Yu Lung
YL
Lyons
Paul A
PA
Smith
Kenneth G C
KG
D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006720:Homozygote; D006723:Hong Kong; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008288:Malaria / Q000235:genetics*; D008969:Molecular Sequence Data; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D017422:Sequence Analysis, DNA; D006113:United Kingdom; D044465:White People / Q000235:genetics
D017931:DNA Primers; C499173:FCGR2B protein, human; D017452:Receptors, IgG
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