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Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production
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نویسنده
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chung s.a. ,taylor k.e. ,graham r.r. ,nititham j. ,lee a.t. ,ortmann w.a. ,jacob c.o. ,alarcón-riquelme m.e. ,tsao b.p. ,harley j.b. ,gaffney p.m. ,moser k.l. ,petri m. ,demirci f.y. ,kamboh m.i. ,manzi s. ,gregersen p.k. ,langefeld c.d. ,behrens t.w. ,criswell l.a.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 3
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چکیده
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Systemic lupus erythematosus (sle) is a clinically heterogeneous,systemic autoimmune disease characterized by autoantibody formation. previously published genome-wide association studies (gwas) have investigated sle as a single phenotype. therefore,we conducted a gwas to identify genetic factors associated with anti-dsdna autoantibody production,a sle-related autoantibody with diagnostic and clinical importance. using two independent datasets,over 400,000 single nucleotide polymorphisms (snps) were studied in a total of 1,717 sle cases and 4,813 healthy controls. anti-dsdna autoantibody positive (anti-dsdna +,n = 811) and anti-dsdna autoantibody negative (anti-dsdna -,n = 906) sle cases were compared to healthy controls and to each other to identify snps associated specifically with these sle subtypes. snps in the previously identified sle susceptibility loci stat4,irf5,itgam,and the major histocompatibility complex were strongly associated with anti-dsdna + sle. far fewer and weaker associations were observed for anti-dsdna - sle. for example,rs7574865 in stat4 had an or for anti-dsdna + sle of 1.77 (95% ci 1.57-1.99,p = 2.0e-20) compared to an or for anti-dsdna - sle of 1.26 (95% ci 1.12-1.41,p = 2.4e-04),with pheterogeneity<0.0005. snps in the sle susceptibility loci bank1,kiaa1542,and ube2l3 showed evidence of association with anti-dsdna + sle and were not associated with anti-dsdna - sle. in conclusion,we identified differential genetic associations with sle based on anti-dsdna autoantibody production. many previously identified sle susceptibility loci may confer disease risk through their role in autoantibody production and be more accurately described as autoantibody propensity loci. lack of strong snp associations may suggest that other types of genetic variation or non-genetic factors such as environmental exposures have a greater impact on susceptibility to anti-dsdna - sle.
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آدرس
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rosalind russell medical research center for arthritis,department of medicine,university of california san francisco,san francisco,ca, United States, rosalind russell medical research center for arthritis,department of medicine,university of california san francisco,san francisco,ca, United States, itgr human genetics,genentech,south san francisco,ca, United States, rosalind russell medical research center for arthritis,department of medicine,university of california san francisco,san francisco,ca, United States, robert s. boas center for genomics and human genetics,feinstein institute for medical research,manhasset,ny, United States, itgr human genetics,genentech,south san francisco,ca, United States, department of medicine,keck school of medicine,university of southern california,los angeles,ca, United States, department of genetics and pathology,uppsala university,uppsala,sweden,andalusian center for genomics and oncological research,pfizer-university of granada-junta de andalucía,granada,spain,arthritis and immunology research program,oklahoma medical research foundation,oklahoma city,ok, United States, department of medicine,university of california los angeles,los angeles,ca, United States, us department of veterans affairs medical center,cincinnati children's hospital medical center,cincinnati,oh, United States, arthritis and immunology research program,oklahoma medical research foundation,oklahoma city,ok, United States, arthritis and immunology research program,oklahoma medical research foundation,oklahoma city,ok, United States, division of rheumatology,johns hopkins university school of medicine,baltimore,md, United States, department of human genetics,graduate school of public health,university of pittsburgh,pittsburgh,pa, United States, department of human genetics,graduate school of public health,university of pittsburgh,pittsburgh,pa, United States, allegheny-singer research institute,pittsburgh,pa, United States, robert s. boas center for genomics and human genetics,feinstein institute for medical research,manhasset,ny, United States, department of biostatistical sciences,wake forest university health sciences,wake forest,nc, United States, itgr human genetics,genentech,south san francisco,ca, United States, rosalind russell medical research center for arthritis,department of medicine,university of california san francisco,san francisco,ca, United States
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Authors
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