Ikari K, Momohara S, Inoue E, Tomatsu T, Hara M, Yamanaka H, Kamatani N
Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada, Tokyo 162-0054, Japan.
Rheumatology (Oxford). 2006 Nov;45(11):1345-8. doi: 10.1093/rheumatology/kel169. Epub 2006 May 11.
The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene is a member of the PTPs that negatively regulate T-cell activation. A missense single nucleotide polymorphism (SNP) in the PTPN22 gene known as R620W was recently reported to be associated with several autoimmune diseases including rheumatoid arthritis (RA). The association was confirmed repeatedly in the populations of North European ancestry. However, the SNP was reported to be non-polymorphic in the Asian populations. Because the gene confers an impact on autoimmune diseases, we attempt to explore an association between PTPN22 gene and RA in a Japanese population without restricting to the SNP, R620W.
We studied 1128 RA patients and 455 controls. In addition to the SNP, R620W, we selected eight testing SNPs spanning 45 kb over the PTPN22 gene using the International HapMap Project. Genotyping was performed using the TaqMan fluorogenic 5' nuclease assay. Associations between RA and each of the SNPs were estimated by the Fisher's exact test. Haplotype was constructed using the expectation-maximization algorithm.
R620W was not polymorphic enough in both the patients and the controls, and was therefore excluded from further analysis. Each allele frequency for the eight other SNPs in both groups was compared and no association was detected. Haplotype analysis also revealed that PTPN22 gene was not associated with RA in a Japanese population.
We found no association between PTPN22 and RA in a Japanese population. The result suggests that the PTPN22 gene is associated with RA only in a specific ethnic group.
蛋白酪氨酸磷酸酶非受体22型（PTPN22）基因是负向调节T细胞活化的蛋白酪氨酸磷酸酶家族成员。最近报道，PTPN22基因中的一个错义单核苷酸多态性（SNP），即R620W，与包括类风湿关节炎（RA）在内的多种自身免疫性疾病相关。该关联在北欧血统人群中得到反复证实。然而，据报道该SNP在亚洲人群中是非多态性的。由于该基因对自身免疫性疾病有影响，我们试图在日本人群中探索PTPN22基因与RA之间的关联，而不限于R620W这个SNP。
我们研究了1128例RA患者和455例对照。除了R620W这个SNP外，我们利用国际人类基因组单体型图计划，在PTPN22基因上选择了跨越45 kb的8个检测SNP。使用TaqMan荧光5'核酸酶分析法进行基因分型。通过Fisher精确检验估计RA与每个SNP之间的关联。使用期望最大化算法构建单倍型。
R620W在患者和对照中多态性都不足，因此被排除在进一步分析之外。比较了两组中其他8个SNP的每个等位基因频率，未检测到关联。单倍型分析也显示，在日本人群中PTPN22基因与RA无关。
我们发现日本人群中PTPN22与RA之间无关联。该结果表明，PTPN22基因仅在特定种族群体中与RA相关。
