Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus
Evidence for CTLA4 as a susceptibility gene for systemic lupus erythematosus
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DOI：
10.1038/sj.ejhg.5201214
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发表时间：
2004-08-01
影响因子：
5.2
通讯作者：
Vicente, AM
中科院分区：
文献类型：
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作者：
Barreto, M;Santos, E;Vicente, AM
几条证据表明细胞毒性T淋巴细胞抗原4（CTLA 4）基因与自身免疫性疾病的易感性有关。我们研究了系统性红斑狼疮（SLE）与CTLA-4基因多态性的关系，这些多态性以前被认为是调节CTLA-4功能的基因：外显子1的+49位的单核苷酸多态性（SNP）和30位非翻译区（3 'UTR）的二核苷酸重复。3 'UTR重复序列显示与SLE显著相关，其中一个等位基因赋予易感性，另一个赋予对疾病的保护。相关的等位基因不支持以前的建议，等位基因大小依赖性的影响，3 'UTR多态性在自身免疫发展，而是表明，它是在连锁不平衡与真正的致病基因座。在我们的人群中未发现外显子1 SNP与SLE相关。鉴于SLE与该多态性相关性的不同研究中获得的相互矛盾的结果，我们进行了一项荟萃分析，包括7项先前发表的研究和本研究。G等位基因携带者和A等位基因携带者SLE的风险分别显著增加和降低。现在需要对疾病相关CTLA 4基因变异体的功能进行表征，以阐明其在SLE和其他自身免疫性疾病发病机制中的作用。欧洲人类遗传学杂志（2004）。
Several lines of evidence implicate the Cytotoxic T Lymphocyte Antigen 4 (CTLA4) gene in susceptibility to autoimmune disease. We have examined the association of systemic lupus erythematosus (SLE) with polymorhisms within the CTLA4 gene that were previously proposed to regulate CTLA-4 function: a single nucleotide polymorphism ( SNP) in position +49 of exon 1 and a dinucleotide repeat in the 30 untranslated region (3'UTR). The 3'UTR repeat showed a significant association with SLE, with one allele conferring susceptibility and another conferring protection to the disease. The associated alleles do not support previous suggestions of an allele size-dependent effect of the 3'UTR polymorphism in autoimmunity development and instead suggest that it is in linkage disequilibrium with a true causative locus. No association of the exon 1 SNP with SLE was found in our population. Given the conflicting results obtained in different studies on the association of SLE with this polymorphism, we performed a meta-analysis including seven previously published studies and the present one. Significantly increased and decreased risks for SLE were found for carriers of the G allele and the A allele, respectively. The functional characterization of disease-associated CTLA4 gene variants is now required to elucidate their role in the pathogenesis of SLE and other autoimmune diseases. European Journal of Human Genetics (2004).