Association of polymorphisms in complement component C3 gene with susceptibility to systemic lupus erythematosus
Association of polymorphisms in complement component C3 gene with susceptibility to systemic lupus erythematosus
复制标题
DOI：
10.1093/rheumatology/kem321
复制
发表时间：
2008-02-01
期刊：
影响因子：
5.5
通讯作者：
Horiuchi, T.
中科院分区：
文献类型：
--
作者：
Miyagawa, H.;Yamai, M.;Horiuchi, T.
客观的。系统性红斑狼疮 (SLE) 相关基因的鉴定。方法。 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、筛选了 C1QA、C1QB、C1QG、C2、MBL2、IGHM、IL-2、IL-4、IL-10、IFNG、TNFA、MAN2A1、TNFRSF11A/RANK、TNFRSF11B/OPG、TNFSF11/OPGL）的单核苷酸多态性 (SNP)，并通过病例对照研究评估了它们与 SLE 的关联。总共纳入了 509 例日裔病例和 964 例对照者。结果。总共鉴定出 316 个 SNP。在日本人群中进行分析时，SLE患者C3基因rs7951位点T和rs2230201位点G的等位基因频率分别为0.110和0.626；显着高于对照组的频率 0.081 和 0.584 [比值比 (OR) 1.40，95% 置信区间 (CI) 1.05-1.86，P=0.016 和 OR=1.19，95% CI= 1.01-1.41，P= 0.038]。在87例有病历的SLE患者中，rs7951 T等位基因携带者的平均血清C3水平显着低于T等位基因非携带者（P=0.0018）。结论。 C3 基因的 rs7951 T 等位基因与 SLE 显着相关，并且 C3 血清水平降低似乎与该等位基因相关。
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 casecontrol 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.