CD28/CTLA4/ICOS 多态性与类风湿关节炎易感性的关联。

Association of the CD28/CTLA4/ICOS polymorphisms with susceptibility to rheumatoid arthritis.

机构信息

Ginseng and Medicinal Plants Research Institute Rural Development Administration, Chungbuk, Korea.

出版信息

Clin Chem Lab Med. 2010 Mar;48(3):345-53. doi: 10.1515/CCLM.2010.074.

DOI:10.1515/CCLM.2010.074

PMID:20113255

Abstract

BACKGROUND

Rheumatoid arthritis (RA) is currently thought to be an immune-mediated disease where the host's genes and environmental factors interact. Some of the immuno-regulatory genes that are responsible for an individual's susceptibility to RA have been identified. The co-stimulatory receptor gene cluster on chromosome 2q33 encodes for both the positive T-cell regulators CD28 molecule (CD28) and inducible T-cell co-stimulator (ICOS), and the negative regulator cytotoxic T-lymphocyte-associated protein 4 (CTLA4). The CTLA4 gene has been implicated in several immune-mediated diseases, but it is not known whether RA is associated with any of these genes.

METHODS

We conducted single nucleotide polymorphism (SNP) genotyping with direct sequencing and restriction fragment length polymorphism for 308 Korean patients with RA and 412 healthy control subjects. For the case-control analysis, SNPStats, SNPAnalyzer and Helixtree programs were used.

RESULTS

Although none of the polymorphisms in CTLA4 showed a significant association with RA, CD28 and ICOS showed a significant association with RA [rs2140148 in CD28, p = 0.022, odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.07-2.40 in the dominant model, rs6726035 in ICOS, p = 0.032, OR = 1.28, 95% CI = 1.02-1.60 in the codominant model].

CONCLUSIONS

Our results suggest that CD28 and ICOS genes may be associated with a risk of RA in Koreans.

摘要

背景

类风湿关节炎（RA）目前被认为是一种免疫介导的疾病，宿主的基因和环境因素相互作用。已经确定了一些负责个体对 RA 易感性的免疫调节基因。染色体 2q33 上的共刺激受体基因簇编码阳性 T 细胞调节剂 CD28 分子（CD28）和诱导性 T 细胞共刺激物（ICOS）以及负调节剂细胞毒性 T 淋巴细胞相关蛋白 4（CTLA4）。CTLA4 基因与多种免疫介导的疾病有关，但尚不清楚 RA 是否与这些基因中的任何一个有关。

方法

我们对 308 名韩国 RA 患者和 412 名健康对照者进行了单核苷酸多态性（SNP）基因分型，直接测序和限制性片段长度多态性。对于病例对照分析，使用了 SNPStats、SNPAnalyzer 和 Helixtree 程序。

结果

尽管 CTLA4 中的任何多态性都与 RA 没有显著关联，但 CD28 和 ICOS 与 RA 有显著关联[CD28 中的 rs2140148，p=0.022，优势比（OR）=1.60，95%置信区间（CI）=1.07-2.40 在显性模型中，ICOS 中的 rs6726035，p=0.032，OR=1.28，95%CI=1.02-1.60 在共显性模型中]。