title: Association of a common complement receptor 2 haplotype with increased risk of systemic lupus erythematosus.
abstract: 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.
authors.affiliation: Division of Rheumatology, University of California-Los Angeles, 1000 Veteran Avenue, Los Angeles, CA 90095, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Susan A
authors.initials: SA
authors.lastname: Boackle
authors.forename: Punchong
authors.initials: P
authors.lastname: Hanvivadhanakul
authors.forename: Daniela
authors.initials: D
authors.lastname: Ulgiati
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Grossman
authors.forename: Youngho
authors.initials: Y
authors.lastname: Lee
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Abraham
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Mercer
authors.forename: Elly
authors.initials: E
authors.lastname: Park
authors.forename: Lee A
authors.initials: LA
authors.lastname: Hebert
authors.forename: Brad H
authors.initials: BH
authors.lastname: Rovin
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Birmingham
authors.forename: Deh-Ming
authors.initials: DM
authors.lastname: Chang
authors.forename: Chung Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Deborah
authors.initials: D
authors.lastname: McCurdy
authors.forename: Humeira M
authors.initials: HM
authors.lastname: Badsha
authors.forename: Bernard Y H
authors.initials: BY
authors.lastname: Thong
authors.forename: Hiok H
authors.initials: HH
authors.lastname: Chng
authors.forename: Frank C
authors.initials: FC
authors.lastname: Arnett
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wallace
authors.forename: C Yung
authors.initials: CY
authors.lastname: Yu
authors.forename: Bevra H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: Betty P
authors.initials: BP
authors.lastname: Tsao
mesh_terms: 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
chemical_list: D017464:Receptors, Complement 3d