Haplotype analysis revealed no association between the PTPN22 gene and RA in a Japanese population
Haplotype analysis revealed no association between the PTPN22 gene and RA in a Japanese population
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DOI：
10.1093/rheumatology/kel169
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发表时间：
2006-11-01
期刊：
影响因子：
5.5
通讯作者：
Kamatani, N.
中科院分区：
文献类型：
--
作者：
Ikari, K.;Momohara, S.;Kamatani, N.
目标。蛋白酪氨酸磷酸酶非受体22 （PTPN22）基因是负性调节t细胞活化的PTPs的一个成员。最近有报道称，PTPN22基因R620W中的错义单核苷酸多态性（SNP）与包括类风湿性关节炎（RA）在内的几种自身免疫性疾病有关。这种联系在北欧血统的人群中反复得到证实。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，我们试图探索日本人群中PTPN22基因与RA之间的关系，而不局限于SNP， r620w .方法。我们研究了1128名RA患者和455名对照者。除了R620W SNP外，我们还使用国际HapMap项目选择了PTPN22基因上的8个测试SNP，跨度为45 kb。采用TaqMan荧光5′核酸酶测定法进行基因分型。RA和每个snp之间的关联通过Fisher的精确检验来估计。利用期望最大化算法构建单倍型。R620W在患者和对照组中都没有足够的多态性，因此被排除在进一步的分析之外。对两组中其他8个snp的等位基因频率进行比较，未发现关联。单倍型分析也显示PTPN22基因与日本人群RA无相关性。我们在日本人群中没有发现PTPN22和RA之间的关联。结果表明，PTPN22基因仅在特定的种族群体中与RA相关。
Objective. 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.Methods. 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.Results. 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.Conclusion. 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.