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Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility
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نویسنده
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zhao j. ,wu h. ,khosravi m. ,cui h. ,qian x. ,kelly j.a. ,kaufman k.m. ,langefeld c.d. ,williams a.h. ,comeau m.e. ,ziegler j.t. ,marion m.c. ,adler a. ,glenn s.b. ,alarcón-riquelme m.e. ,biolupus network division of rheumatology ,genles network division of rheumatology ,pons-estel b.a. ,harley j.b. ,bae s.-c. ,bang s.-y. ,cho s.-k. ,jacob c.o. ,vyse t.j. ,niewold t.b. ,gaffney p.m. ,moser k.l. ,kimberly r.p. ,edberg j.c. ,brown e.e. ,alarcon g.s. ,petri m.a. ,ramsey-goldman r. ,vilá l.m. ,reveille j.d. ,james j.a. ,gilkeson g.s. ,kamen d.l. ,freedman b.i. ,anaya j.-m. ,merrill j.t. ,criswell l.a. ,scofield r.h. ,stevens a.m. ,guthridge j.m. ,chang d.-m. ,song y.w. ,park j.a. ,lee e.y. ,boackle s.a. ,grossman j.m. ,hahn b.h. ,goodship t.h.j. ,cantor r.m. ,yu c.-y. ,shen n. ,tsao b.p.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 5
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چکیده
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Systemic lupus erythematosus (sle),a complex polygenic autoimmune disease,is associated with increased complement activation. variants of genes encoding complement regulator factor h (cfh) and five cfh-related proteins (cfhr1-cfhr5) within the chromosome 1q32 locus linked to sle,have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to sle. we assessed 60 snps covering the cfh-cfhrs region for association with sle in 15,864 case-control subjects derived from four ethnic groups. significant allelic associations with sle were detected in european americans (ea) and african americans (aa),which could be attributed to an intronic cfh snp (rs6677604,in intron 11,pmeta = 6.6×10-8,or = 1.18) and an intergenic snp between cfhr1 and cfhr4 (rs16840639,pmeta = 2.9×10-7,or = 1.17) rather than to previously identified disease-associated cfh exonic snps,including i62v,y402h,a474a,and d936e. in addition,allelic association of rs6677604 with sle was subsequently confirmed in asians (as). haplotype analysis revealed that the underlying causal variant,tagged by rs6677604 and rs16840639,was localized to a ~146 kb block extending from intron 9 of cfh to downstream of cfhr1. within this block,the deletion of cfhr3 and cfhr1 (cfhr3-1δ),a likely causal variant measured using multiplex ligation-dependent probe amplification,was tagged by rs6677604 in ea and as and rs16840639 in aa,respectively. deduced from genotypic associations of tag snps in ea,aa,and as,homozygous deletion of cfhr3-1δ (pmeta = 3.2×10-7,or = 1.47) conferred a higher risk of sle than heterozygous deletion (pmeta = 3.5×10-4,or = 1.14). these results suggested that the cfhr3-1δ deletion within the sle-associated block,but not the previously described exonic snps of cfh,might contribute to the development of sle in ea,aa,and as,providing new insights into the role of complement regulators in the pathogenesis of sle.
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آدرس
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division of rheumatology,department of medicine,david geffen school of medicine,university of california los angeles,los angeles,ca, United States, division of rheumatology,department of medicine,david geffen school of medicine,university of california los angeles,los angeles,ca, United States, division of rheumatology,department of medicine,david geffen school of medicine,university of california los angeles,los angeles,ca, United States, joint molecular rheumatology laboratory of institute of health sciences,shanghai renji hospital,shanghai jiao tong university school of medicine,shanghai institutes for biological sciences,chinese academy of sciences,shanghai, China, joint molecular rheumatology laboratory of institute of health sciences,shanghai renji hospital,shanghai jiao tong university school of medicine,shanghai institutes for biological sciences,chinese academy of sciences,shanghai, China, arthritis and clinical immunology research program,oklahoma medical research foundation,oklahoma city,ok, United States, arthritis and clinical immunology research program,oklahoma medical research foundation,oklahoma city,ok,united states,united states department of veterans affairs medical center,oklahoma city,ok, United States, department of biostatistical sciences,wake forest university health sciences,wake forest,nc, United States, department of biostatistical sciences,wake forest university health sciences,wake forest,nc, United States, department of biostatistical sciences,wake forest university health sciences,wake forest,nc, United States, department of biostatistical sciences,wake forest university health sciences,wake forest,nc, United States, department of biostatistical sciences,wake forest university health sciences,wake forest,nc, United States, arthritis and clinical immunology research program,oklahoma medical research foundation,oklahoma city,ok, United States, arthritis and clinical immunology research program,oklahoma medical research foundation,oklahoma city,ok, United States, arthritis and clinical immunology research program,oklahoma medical research foundation,oklahoma city,ok,united states,center for genomics and oncological research,pfizer-university of granada-junta de andalucia,granada, Spain, department of medicine,david geffen school of medicine,university of california los angeles,los angeles,ca, United States, department of medicine,david geffen school of medicine,university of california los angeles,los angeles,ca, United States, sanatorio parque,rosario, Argentina, cincinnati children's hospital medical center,cincinnati,oh,united states,united states department of veterans affairs medical center,cincinnati,oh, United States, department of rheumatology,hanyang university hospital for rheumatic diseases,seoul, South Korea, department of rheumatology,hanyang university hospital for rheumatic diseases,seoul, South Korea, department of rheumatology,hanyang university hospital for rheumatic diseases,seoul, South Korea, department of medicine,keck school of medicine,university of southern california,los angeles,ca, United States, divisions of genetics and molecular medicine and immunology,king's college london,london, United Kingdom, section of rheumatology,gwen knapp center for lupus and immunology research,university of chicago,chicago,il, United States, arthritis and clinical immunology research program,oklahoma medical research foundation,oklahoma city,ok, United States, arthritis and clinical immunology research program,oklahoma medical research foundation,oklahoma city,ok, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al,united states,department of epidemiology,university of alabama at birmingham,birmingham,al, United States, department of medicine,university of alabama at birmingham,birmingham,al, United States, department of medicine,johns hopkins university school of medicine,baltimore,md, United States, division of rheumatology,feinberg school of medicine,northwestern university,chicago,il, United States, division of rheumatology,department of medicine,university of puerto rico medical sciences campus,san juan, Puerto Rico, rheumatology and clinical immunogenetics,university of texas health science center at houston,houston,tx, United States, arthritis and clinical immunology research program,oklahoma medical research foundation,oklahoma city,ok,united states,department of medicine,university of oklahoma health sciences center,oklahoma city,ok, United States, division of rheumatology,medical university of south carolina,charleston,sc, United States, division of rheumatology,medical university of south carolina,charleston,sc, United States, department of internal medicine,wake forest university health sciences,winston-salem,nc, United States, center for autoimmune disease research,universidad del rosario,bogota, Colombia, clinical pharmacology,oklahoma medical research foundation,oklahoma city,ok, United States, rosalind russell medical research center for arthritis,department of medicine,university of california san francisco,san francisco,ca, United States, arthritis and clinical immunology research program,oklahoma medical research foundation,oklahoma city,ok,united states,united states department of veterans affairs medical center,oklahoma city,ok,united states,department of medicine,university of oklahoma health sciences center,oklahoma city,ok, United States, division of rheumatology,department of pediatrics,university of washington,seattle,wa,united states,center for immunity and immunotherapies,seattle children's research institute,seattle,wa, United States, arthritis and clinical immunology research program,oklahoma medical research foundation,oklahoma city,ok, United States, national defense medical center,taipei, Taiwan, division of rheumatology,seoul national university,seoul, South Korea, division of rheumatology,seoul national university,seoul, South Korea, division of rheumatology,seoul national university,seoul, South Korea, division of rheumatology,school of medicine,university of colorado denver,aurora,co, United States, division of rheumatology,department of medicine,david geffen school of medicine,university of california los angeles,los angeles,ca, United States, division of rheumatology,department of medicine,david geffen school of medicine,university of california los angeles,los angeles,ca, United States, institute of human genetics,newcastle university,newcastle upon tyne, United Kingdom, department of human genetics,university of california los angeles,los angeles,ca, United States, department of pediatrics,the ohio state university,columbus,oh, United States, joint molecular rheumatology laboratory of institute of health sciences,shanghai renji hospital,shanghai jiao tong university school of medicine,shanghai institutes for biological sciences,chinese academy of sciences,shanghai, China, division of rheumatology,department of medicine,david geffen school of medicine,university of california los angeles,los angeles,ca, United States
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Authors
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