title: Association of polymorphisms in complement component C3 gene with susceptibility to systemic lupus erythematosus.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Miyagawa
authors.forename: M
authors.initials: M
authors.lastname: Yamai
authors.forename: D
authors.initials: D
authors.lastname: Sakaguchi
authors.forename: C
authors.initials: C
authors.lastname: Kiyohara
authors.forename: H
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kimoto
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: J-H
authors.initials: JH
authors.lastname: Lee
authors.forename: C-Y
authors.initials: CY
authors.lastname: Tsai
authors.forename: B-L
authors.initials: BL
authors.lastname: Chiang
authors.forename: T
authors.initials: T
authors.lastname: Shimoda
authors.forename: M
authors.initials: M
authors.lastname: Harada
authors.forename: T
authors.initials: T
authors.lastname: Tahira
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Horiuchi
mesh_terms: D003176:Complement C3 / Q000235:genetics*; D003165:Complement System Proteins / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000276:immunology; D005091:Exons; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007378:Interleukins / Q000235:genetics; D007564:Japan; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic
chemical_list: D003176:Complement C3; D007378:Interleukins; D003165:Complement System Proteins; D004247:DNA