CTLA-4单核苷酸多态性与中国汉族人类风湿关节炎的关联分析

目的在中国汉族类风湿关节炎（RA）患者中，检测细胞毒T淋巴细胞相关抗原4（CTLA-4）基因中的单核苷酸多态性（SNPs）并进行关联分析。方法用变性梯度凝胶电泳法（DGGE）在326例RA患者和250名健康志愿者提供的血样中检测CTLA-4基因的SNPs（MH30，＋49，CT60和J031）．分析单个位点的等位基因和基因型频率是否与RA相关。结果在RA患者中，CTLA-4的＋49和CT60的等位基因频率及它们的基因型频率显著高于健康对照组（P=0.028和0．007）；此两种SNPs构成的4种单倍体的分布状态两组间差异有统计学意义（x^2=10．58，d．f=3，P=-0．014）。结论CTLA-4基因上2个SNPs及单倍体型与中国汉族RA之间存在显著的相关性。

Association between single nucleotide polymorphism in cytotoxic T lymphocyte-associated antigen 4 gene and rheumatoid arthritis in Chinese Han nationality

Objective To examine the single nudeotide polymorphisms (SNPs) in cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene in Chinese Han nationality with rheumatoid arthritis (RA). Methods The denaturing gradient gel electrophoresis (DGGE) was used to genotype the polymorphisms of four SNPs (MH30,+49, CT60 and JO31) of the CTLA-4 gene in 326 RA patients and 250 healthy controls. Furthermore, meta-analysis of all available studies relating +49 polymorphism to the risk of RA was performed to confirm the disease association. Results Among the SNPs examined, the genotype frequencies of CTLA-4 +49 and CT60 in RA patients differed significantly from controls (P=0.028 and 0.007). In addition, the distribution of the four haplotypes constructed by these two SNPs was significantly different between patients and controls (X2=10.58,d.f=3,P=0.014). Conclusion These results suggest that the CTLA-4 gene may be involved in the susceptibility to RA in Chinese Han nationality and both +49 and CT60 of CTLA-4 gene may be the causal variants in RA.