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 (nonpara...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 104; no. 10; pp. 3961 - 3966
Main Authors Wu, Hui, Boackle, Susan A, Hanvivadhanakul, Punchong, Ulgiati, Daniela, Grossman, Jennifer M, Lee, Youngho, Shen, Nan, Abraham, Lawrence J, Mercer, Timothy R, Park, Elly, Hebert, Lee A, Rovin, Brad H, Birmingham, Dan J, Chang, Deh-Ming, Chen, Chung Jen, McCurdy, Deborah, Badsha, Humeira M, Thong, Bernard Y.H, Chng, Hiok H, Arnett, Frank C, Wallace, Daniel J, Yu, C. Yung, Hahn, Bevra H, Cantor, Rita M, Tsao, Betty P
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 06.03.2007
National Acad Sciences
Subjects
Arthritis
Asian Continental Ancestry Group
Biological Sciences
China
Chromosomes
Computer software
European Continental Ancestry Group
Exons
Family Health
Female
Genes
Genetic Linkage
Genetic loci
Genetic Predisposition to Disease
Genomics
Haplotypes
Humans
Lupus
Lupus Erythematosus, Systemic - ethnology
Lupus Erythematosus, Systemic - genetics
Male
Messenger RNA
Microsatellite Repeats
Pathology
Polymorphism
Polymorphism, Single Nucleotide
Receptors, Complement 3d - genetics
Risk
Risk factors
Rodents
Skin diseases
Systemic lupus erythematosus
White people
China
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Summary: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.
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Author contributions: H.W., S.A.B., P.H., and D.U. contributed equally to this work; S.A.B., D.U., and B.P.T. designed research; H.W., P.H., D.U., J.M.G., Y.L., N.S., L.J.A., T.R.M., E.P., L.A.H., B.H.R., D.J.B., D.-M.C., C.J.C., D.M., H.M.B., B.Y.H.T., and H.H.C. performed research; J.M.G., N.S., L.A.H., B.H.R., D.J.B., D.-M.C., C.J.C., D.M., H.M.B., B.Y.H.T., H.H.C., F.C.A., D.J.W., C.Y.Y, and B.H.H. contributed new reagents/analytic tools; H.W., S.A.B., D.U., R.M.C., and B.P.T. analyzed data; and H.W., S.A.B., D.U., F.C.A., D.J.W., C.Y.Y., B.H.H., and B.P.T. wrote the paper.
Edited by Ernest Beutler, The Scripps Research Institute, La Jolla, CA, and approved December 28, 2006
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0609101104