Association of polymorphisms in complement component C3 gene with susceptibility to systemic lupus erythematosus.
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.
Miyagawa
H
H
Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Yamai
M
M
Sakaguchi
D
D
Kiyohara
C
C
Tsukamoto
H
H
Kimoto
Y
Y
Nakamura
T
T
Lee
J-H
JH
Tsai
C-Y
CY
Chiang
B-L
BL
Shimoda
T
T
Harada
M
M
Tahira
T
T
Hayashi
K
K
Horiuchi
T
T
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
D003176:Complement C3; D007378:Interleukins; D003165:Complement System Proteins; D004247:DNA