Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus.
A genomic region on distal mouse chromosome 1 and its syntenic human counterpart 1q23-42 show strong evidence of harboring lupus susceptibility genes. We found evidence of linkage at 1q32.2 in a targeted genome scan of 1q21-43 in 126 lupus multiplex families containing 151 affected sibpairs (nonparametric linkage score 2.52, P = 0.006). A positional candidate gene at 1q32.2, complement receptor 2 (CR2), is also a candidate in the murine Sle1c lupus susceptibility locus. To explore its role in human disease, we analyzed 1,416 individuals from 258 Caucasian and 142 Chinese lupus simplex families and demonstrated that a common three-single-nucleotide polymorphism CR2 haplotype (rs3813946, rs1048971, rs17615) was associated with lupus susceptibility (P = 0.00001) with a 1.54-fold increased risk for the development of disease. Single-nucleotide polymorphism 1 (rs3813946), located in the 5' untranslated region of the CR2 gene, altered transcriptional activity, suggesting a potential mechanism by which CR2 could contribute to the development of lupus. Our findings reveal that CR2 is a likely susceptibility gene for human lupus at 1q32.2, extending previous studies suggesting that CR2 participates in the pathogenesis of systemic lupus erythematosus.
Wu
Hui
H
Division of Rheumatology, University of California-Los Angeles, 1000 Veteran Avenue, Los Angeles, CA 90095, USA.
Boackle
Susan A
SA
Hanvivadhanakul
Punchong
P
Ulgiati
Daniela
D
Grossman
Jennifer M
JM
Lee
Youngho
Y
Shen
Nan
N
Abraham
Lawrence J
LJ
Mercer
Timothy R
TR
Park
Elly
E
Hebert
Lee A
LA
Rovin
Brad H
BH
Birmingham
Dan J
DJ
Chang
Deh-Ming
DM
Chen
Chung Jen
CJ
McCurdy
Deborah
D
Badsha
Humeira M
HM
Thong
Bernard Y H
BY
Chng
Hiok H
HH
Arnett
Frank C
FC
Wallace
Daniel J
DJ
Yu
C Yung
CY
Hahn
Bevra H
BH
Cantor
Rita M
RM
Tsao
Betty P
BP
D044466:Asian People; D002681:China; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology* / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide; D017464:Receptors, Complement 3d / Q000235:genetics*; D012306:Risk; D044465:White People
D017464:Receptors, Complement 3d