RESEARCH - Association of polymorphisms in complement component C3 gene with susceptibility to SLE

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Rheumatology Advance Access published online on January 3, 2008

Rheumatology, doi:10.1093/rheumatology/kem321

Association of polymorphisms in complement component C3 gene with

susceptibility to systemic lupus erythematosus

H. Miyagawa1, M. Yamai2, D. Sakaguchi2, C. Kiyohara3, H. Tsukamoto1, Y.

Kimoto1, T. Nakamura4, J.-H. Lee5, C.-Y. Tsai6, B.-L. Chiang5, T. Shimoda7,

M. Harada1, T. Tahira2, K. Hayashi2 and T. Horiuchi1

1Department of Medicine and Biosystemic Science, Graduate School of Medical

Sciences, 2Medical Institute of Bioregulation, 3Department of Preventive

Medicine, Graduate School of Medical Sciences, Kyushu University, 4Kumamoto

Center for Arthritis and Rheumatology, Kumamoto, Japan, 5Department of

Pediatrics, National Taiwan University Hospital, 6Department of Medicine,

Taipei Veterans General Hospital and National Yang-Ming University School of

Medicine, Taipei, Taiwan and 7Department of Clinical Research, Fukuoka

National Hospital, Fukuoka, Japan.

Abstract

Objective. Identification of the genes responsible for systemic lupus

erythematosus (SLE).

Methods. All the exons and putative promoter regions of 53 candidate genes

(TNFRSF6/Fas, TNFSF6/FasL, Fli1, TNFSF10/TRAIL, TNFSF12/TWEAK, Bcl-2, PTEN,

FADD, TRADD, CDKN1A, TNFRSF1A/TNFR1, TNFRSF4/OX40, TNFSF4/OX40L,

TNFSF5/CD40L, TNFSF13B/BAFF, ICOS, CTLA4, CD28, FYN, G2A, CR2, PTPRC/CD45,

CD22, CD19, Lyn, PDCD1, PTPN6, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, TGFBR3,

CD3Z, DNASE1, APCS, MERTK, C3, C1QA, C1QB, C1QG, C2, MBL2, IGHM, IL-2, IL-4,

IL-10, IFNG, TNFA, MAN2A1, TNFRSF11A/RANK, TNFRSF11B/OPG, TNFSF11/OPGL) were

screened for single nucleotide polymorphisms (SNPs) and their association

with SLE was assessed by case-control studies. A total of 509 cases and 964

controls of Japanese descent were enrolled.

Results. A total of 316 SNPs was identified. When analysed in the Japanese

population, the allele frequencies of T at rs7951 and G at rs2230201 of the

C3 gene were 0.110 and 0.626, respectively, in SLE patients; significantly

higher than the frequencies of 0.081 and 0.584, respectively, in controls

[odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.05-1.86, P = 0.016

and OR=1.19, 95% CI = 1.01-1.41, P = 0.038, respectively]. The mean serum C3

level of carriers of the rs7951 T allele was significantly lower than that

of non-carriers of the T allele in 87 SLE patients whose medical records

were available (P = 0.0018).

Conclusion. rs7951 T allele of the C3 gene was significantly associated with

SLE, and decreased serum level of C3 seems to be correlated with this

allele.

http://rheumatology.oxfordjournals.org/cgi/content/abstract/kem321v1?papetoc

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