Recent advances in the genetics of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of antinuclear autoantibodies and the inflammatory infiltration of many organ systems. SLE is a complex disorder in which multiple genetic variants, together with environmental and hormonal factors, contribute to disease risk. In this article, we summarize our current understanding of the genetic contribution to SLE in light of recent genome-wide association studies, which have brought the total number of confirmed SLE susceptibility loci to 29. In the second section, we explore the functional implications of these risk loci and, in particular, highlight the role that many of these genes play in the Toll-like receptor and type I interferon signaling pathways. Finally, we discuss the genetic overlap between SLE and other autoimmune and inflammatory conditions as several risk loci are shared among multiple disorders, suggesting common underlying pathogenic mechanisms.
Flesher
Donna L Thibault
DL
ITGR Human Genetics, Genentech Research & Early Development, 1 DNA Way, South San Francisco, CA 94080-94990, USA.
Sun
Xin
X
Behrens
Timothy W
TW
Graham
Robert R
RR
Criswell
Lindsey A
LA
D000328:Adult; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D012307:Risk Factors; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology; D055815:Young Adult
D001323:Autoantibodies; D007370:Interferon Type I; D051193:Toll-Like Receptors