日本人群中CTLA-4基因多态性而非CD28基因多态性与系统性红斑狼疮的关联。

Association of CTLA-4 but not CD28 gene polymorphisms with systemic lupus erythematosus in the Japanese population.

作者信息

Ahmed S, Ihara K, Kanemitsu S, Nakashima H, Otsuka T, Tsuzaka K, Takeuchi T, Hara T

机构信息

Departments of Pediatrics and. Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Rheumatology (Oxford). 2001 Jun;40(6):662-7. doi: 10.1093/rheumatology/40.6.662.

DOI:10.1093/rheumatology/40.6.662

PMID:11426024

Abstract

OBJECTIVE

Systemic lupus erythematosus (SLE) in a multisystem autoimmune disorder characterized by multiorgan pathology and autoantibodies against a variety of autoantigens. The CD28 and CTLA-4 genes might be candidate genes for SLE, because costimulation signals from CD80/CD86 to CD28/CTLA-4 have been suggested to play an important role in the activation or inactivation of T lymphocytes.

METHODS

We investigated three polymorphic regions within the CTLA-4 gene, a C/T base exchange in the promoter region -318 (CTLA-4 -318C/T), an A/G substitution in the exon 1 position 49 (CTLA-4 49A/G), an (AT)(n) repeat polymorphism in the 3' untranslated region of exon 4 [CTLA-4 3' (AT)(n)], and a CD28 gene polymorphism, a T/C substitution in the intron 3 position +17 (CD28 IVS3+17T/C), in SLE patients and controls.

RESULTS

SLE patients had significantly higher frequencies of the CTLA-4 49G allele (P=0.003) and of the CTLA-4 (AT)(n) 106 bp allele (P=0.0008) than controls. We also found a strong linkage disequilibrium between the A allele of CTLA-4 49A/G and the 86 bp allele of CTLA-4 3' (AT)(n). On the contrary, no association was found between SLE and CTLA-4 -318C/T or CD28 IVS3 +17T/C.

CONCLUSION

We conclude that the CTLA-4 gene appears to play a significant role in the development of SLE in the Japanese population.

摘要

目的

系统性红斑狼疮（SLE）是一种多系统自身免疫性疾病，其特征为多器官病变以及针对多种自身抗原的自身抗体。CD28和CTLA-4基因可能是SLE的候选基因，因为从CD80/CD86到CD28/CTLA-4的共刺激信号已被认为在T淋巴细胞的激活或失活中起重要作用。

方法

我们研究了CTLA-4基因内的三个多态性区域，即启动子区域-318处的C/T碱基交换（CTLA-4 -318C/T）、外显子1位置49处的A/G替换（CTLA-4 49A/G）、外显子4的3'非翻译区的(AT)(n)重复多态性[CTLA-4 3'(AT)(n)]，以及CD28基因多态性，即内含子3位置+17处的T/C替换（CD28 IVS3+17T/C），对SLE患者和对照组进行了研究。

结果

SLE患者中CTLA-4 49G等位基因（P=0.003）和CTLA-4 (AT)(n) 106 bp等位基因（P=0.0008）的频率显著高于对照组。我们还发现CTLA-4 49A/G的A等位基因与CTLA-4 3'(AT)(n)的86 bp等位基因之间存在强连锁不平衡。相反，未发现SLE与CTLA-4 -318C/T或CD28 IVS3 +17T/C之间存在关联。