Association of polymorphisms in complement component C3 gene with susceptibility to systemic lupus erythematosus
Journal
Rheumatology
Journal Volume
47
Journal Issue
2
Pages
158-164
Date Issued
2008
Author(s)
Miyagawa H.
Yamai M.
Sakaguchi D.
Kiyohara C.
Tsukamoto H.
Kimoto Y.
Nakamura T.
Tsai C.-Y.
Shimoda T.
Harada M.
Tahira T.
Hayashi K.
Horiuchi T.
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. ? The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
SDGs
Other Subjects
CD134 antigen; CD28 antigen; CD40 ligand; complement component C3; cyclin dependent kinase inhibitor 1A; cytotoxic T lymphocyte antigen 4; deoxyribonuclease I; Fas antigen; Fas associated death domain protein; Fas ligand; interleukin 10; interleukin 2; interleukin 4; mannose binding lectin 2; osteoclast differentiation factor; osteoprotegerin; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; protein bcl 2; protein kinase Fyn; transcription factor Fli 1; tumor necrosis factor receptor 1; tumor necrosis factor related apoptosis inducing ligand; article; case control study; confidence interval; controlled study; exon; female; gene frequency; gene function; gene locus; gene mutation; gene sequence; genetic analysis; genetic identification; genetic polymorphism; genetic screening; genetic susceptibility; genotype; human; immunopathogenesis; Japanese; major clinical study; male; nucleotide sequence; priority journal; promoter region; protein blood level; risk factor; single nucleotide polymorphism; systemic lupus erythematosus; Complement C3; Complement System Proteins; DNA; Exons; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Interleukins; Japan; Lupus Erythematosus, Systemic; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Polymorphism, Single-Stranded Conformational; Promoter Regions (Genetics)
Type
journal article