A targeted association study in systemic lupus erythematosus identifies multiple susceptibility alleles.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Multiple genetic and environmental factors contribute to the pathogenesis of this disease. Recent genome-wide association studies have added substantially to the number of genes associated with SLE. To replicate some of these susceptibility loci, single-nucleotide polymorphisms reported to be associated to SLE were evaluated in a cohort of 245 well-phenotyped Canadian SLE trios. Our results replicate previously reported associations to alleles of interferon regulatory factor 5 (IRF5), major histocompatibility complex (MHC), tumor necrosis factor (ligand) superfamily member 4 (TNFSF4), Kell blood group complex subunit-related family member 6 (XKR6), B-cell scaffold protein with ankyrin repeats 1 (BANK1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), ubiquitin-conjugating enzyme E2L 3 (UBE2L3) and islet cell autoantigen 1 (ICA1). We also identify putative associations to cytotoxic T-lymphocyte-associated protein 4 (CTLA4), a gene associated with several autoimmune disorders, and ERBB3, a locus on 12q13 that was previously reported to be associated with type 1 diabetes. This study confirms the existence of multiple genetic risk factors for SLE, and supports the notion that some risk factors for SLE are shared with other inflammatory disorders.
Budarf
M L
ML
Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.
Goyette
P
P
Boucher
G
G
Lian
J
J
Graham
R R
RR
Claudio
J O
JO
Hudson
T
T
Gladman
D
D
Clarke
A E
AE
Pope
J E
JE
Peschken
C
C
Smith
C D
CD
Hanly
J
J
Rich
E
E
Boire
G
G
Barr
S G
SG
Zummer
M
M
Fortin
P R
PR
Wither
J
J
Rioux
J D
JD
D001327:Autoimmune Diseases / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide