Miyagawa H, Yamai M, Sakaguchi D, Kiyohara C, Tsukamoto H, Kimoto Y, Nakamura T, Lee J-H, Tsai C-Y, Chiang B-L, Shimoda T, Harada M, Tahira T, Hayashi K, Horiuchi T
Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Rheumatology (Oxford). 2008 Feb;47(2):158-64. doi: 10.1093/rheumatology/kem321. Epub 2008 Jan 3.
Identification of the genes responsible for systemic lupus erythematosus (SLE).
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.
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).
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.
鉴定导致系统性红斑狼疮（SLE）的基因。
对53个候选基因（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）的所有外显子和假定的启动子区域进行单核苷酸多态性（SNP）筛查，并通过病例对照研究评估其与SLE的关联。共纳入了509例日本血统的病例和964例对照。
共鉴定出316个SNP。在日本人群中进行分析时，C3基因rs7951位点的T等位基因和rs2230201位点的G等位基因在SLE患者中的频率分别为0.110和0.626，显著高于对照组中分别为=0.081和0.584的频率[优势比（OR）=1.40，95%置信区间（CI）=1.05 - 1.86，P = =0.016；OR = 1.19，95%CI = 1.01 - 1.41，P = =0.038]。在有病历记录的87例SLE患者中，rs7951 T等位基因携带者的平均血清C3水平显著低于非T等位基因携带者（P = =0.0018）。
C3基因的rs7951 T等位基因与SLE显著相关，血清C3水平降低似乎与该等位基因有关。
