title: A defunctioning polymorphism in FCGR2B is associated with protection against malaria but susceptibility to systemic lupus erythematosus.
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.
authors.affiliation: Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 0XY, United Kingdom.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Willcocks
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Carr
authors.forename: Heather A
authors.initials: HA
authors.lastname: Niederer
authors.forename: Tim F
authors.initials: TF
authors.lastname: Rayner
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Williams
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
authors.forename: J Anthony G
authors.initials: JA
authors.lastname: Scott
authors.forename: Britta C
authors.initials: BC
authors.lastname: Urban
authors.forename: Norbert
authors.initials: N
authors.lastname: Peshu
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Yu Lung
authors.initials: YL
authors.lastname: Lau
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lyons
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
mesh_terms: 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
chemical_list: D017931:DNA Primers; C499173:FCGR2B protein, human; D017452:Receptors, IgG
references.citation: Infect Immun. 1991 Sep;59(9):3280-3
references.pmid: 1879941
references.citation: Hum Mol Genet. 2005 Oct 1;14(19):2881-92
references.pmid: 16115811
references.citation: Cell. 1996 May 3;85(3):303-6
references.pmid: 8616885
references.citation: Infect Immun. 2000 Oct;68(10):5724-30
references.pmid: 10992477
references.citation: Blood. 2005 Jul 1;106(1):368-71
references.pmid: 15769889
references.citation: J Exp Med. 1996 Aug 1;184(2):557-67
references.pmid: 8760809
references.citation: J Exp Med. 2004 Mar 1;199(5):717-23
references.pmid: 14981111
references.citation: Science. 2000 Oct 6;290(5489):84-9
references.pmid: 11021804
references.citation: Arthritis Rheum. 1982 Nov;25(11):1271-7
references.pmid: 7138600
references.citation: Nat Rev Genet. 2009 May;10(5):285-90
references.pmid: 19337289
references.citation: Science. 2005 Jan 28;307(5709):590-3
references.pmid: 15681388
references.citation: J Infect Dis. 2004 Aug 1;190(3):439-47
references.pmid: 15243915
references.citation: Control Clin Trials. 1986 Sep;7(3):177-88
references.pmid: 3802833
references.citation: Tissue Antigens. 2004 Jan;63(1):21-7
references.pmid: 14651519
references.citation: Tissue Antigens. 2003 May;61(5):374-83
references.pmid: 12753656
references.citation: Arthritis Rheum. 2002 May;46(5):1242-54
references.pmid: 12115230
references.citation: Arthritis Rheum. 2003 Nov;48(11):3242-52
references.pmid: 14613290
references.citation: Arthritis Rheum. 2006 Dec;54(12):3908-17
references.pmid: 17133600
references.citation: N Engl J Med. 1989 Jun 15;320(24):1586-91
references.pmid: 2657427
references.citation: Nat Med. 2005 Oct;11(10):1056-8
references.pmid: 16170323
references.citation: Hum Genet. 2005 Jul;117(2-3):220-7
references.pmid: 15895258
references.citation: Immunogenetics. 2000 May;51(6):429-35
references.pmid: 10866109
references.citation: N Engl J Med. 2005 Jan 6;352(1):39-47
references.pmid: 15635111
references.citation: J Clin Invest. 1995 May;95(5):2315-23
references.pmid: 7738194
references.citation: J Exp Med. 2008 Apr 14;205(4):883-95
references.pmid: 18362174
references.citation: Immunity. 2000 Aug;13(2):277-85
references.pmid: 10981970
references.citation: J Infect Dis. 2005 Jul 1;192(1):178-86
references.pmid: 15942909
references.citation: Cell Immunol. 2001 Mar 15;208(2):73-9
references.pmid: 11333139
references.citation: Lupus. 2006;15(11):715-9
references.pmid: 17153840
references.citation: Arthritis Rheum. 2004 Apr;50(4):1348-50
references.pmid: 15077320
references.citation: Am J Hum Genet. 2005 Aug;77(2):171-92
references.pmid: 16001361
references.citation: Curr Biol. 2000 Feb 24;10(4):227-30
references.pmid: 10704418
references.citation: Arthritis Rheum. 2005 Apr;52(4):1138-47
references.pmid: 15818688
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7169-74
references.pmid: 17435165
references.citation: Nat Genet. 2008 Jan;40(1):83-9
references.pmid: 18059267
references.citation: Trends Parasitol. 2008 Jul;24(7):291-2
references.pmid: 18467175
references.citation: Bull World Health Organ. 2006 Mar;84(3):181-8
references.pmid: 16583076