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

Wu H,Boackle SA,Hanvivadhanakul P,Ulgiati D,Grossman JM,Lee Y,Shen N,Abraham LJ,Mercer TR,Park E,Hebert LA,Rovin BH,Birmingham DJ,Chang DM,Chen CJ,McCurdy D,Badsha HM,Thong BY,Chng HH,Arnett FC,Wallace DJ,Yu CY

doi

10.1073/pnas.0609101104

subject

Has Abstract

pub_date

2007-03-06 00:00:00

pages

3961-6

issue

10

eissn

0027-8424

issn

1091-6490

pii

0609101104

journal_volume

104

pub_type

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