Lee Hye-Soon, Korman Benjamin D, Le Julie M, Kastner Daniel L, Remmers Elaine F, Gregersen Peter K, Bae Sang-Cheol
Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Seoul, South Korea.
Arthritis Rheum. 2009 Feb;60(2):364-71. doi: 10.1002/art.24245.
Recent studies have identified a number of novel rheumatoid arthritis (RA) susceptibility loci in Caucasian populations. The aim of this study was to determine whether the genetic variants at 4q27, 6q23, CCL21, TRAF1/C5, and CD40 identified in Caucasians are also associated with RA in a Korean case-control collection. We also comprehensively evaluated the genetic variation within PTPN22, a well-established autoimmune disease-associated gene.
We designed an experiment to thoroughly evaluate the PTPN22 linkage disequilibrium region, using tag single-nucleotide polymorphisms (SNPs) and disease-associated SNPs at 5 RA-associated loci recently identified in Caucasians, in 1,128 Korean patients with RA and 1,022 ethnically matched control subjects. We also resequenced the PTPN22 gene to seek novel coding variants that might be contributing to disease in this population.
None of the susceptibility loci identified in Caucasian patients with RA contributed significantly to disease in Koreans. Although tag SNPs covering the PTPN22 linkage disequilibrium block were polymorphic, they did not reveal any disease association, and resequencing did not identify any new common coding region variants in this population. The 6q23 and 4q27 SNPs assayed were nonpolymorphic in this population, and the TRAF1/C5, CD40, and CCL21 SNPs did not show any evidence for association with RA in this population of Korean patients.
The genetic risk factors for RA are different in Caucasian and Korean patients. Although patients of different ethnic groups share the HLA region as a major genetic risk locus, most other genes shown to be significantly associated with disease in Caucasians appear not to play a role in Korean patients with RA.
近期研究已在白种人群体中确定了多个新的类风湿关节炎（RA）易感基因座。本研究的目的是确定在白种人中鉴定出的位于4q27、6q23、CCL21、TRAF1/C5和CD40的基因变异在韩国病例对照样本中是否也与RA相关。我们还全面评估了已明确的自身免疫性疾病相关基因PTPN22内的基因变异。
我们设计了一项实验，使用标签单核苷酸多态性（SNP）以及最近在白种人中确定的5个RA相关基因座处的疾病相关SNP，对1128例韩国RA患者和1022例种族匹配的对照受试者进行PTPN22连锁不平衡区域的全面评估。我们还对PTPN22基因进行重测序，以寻找可能导致该人群发病的新编码变异。
在白种RA患者中鉴定出的易感基因座均未对韩国人的疾病产生显著影响。虽然覆盖PTPN22连锁不平衡区域的标签SNP具有多态性，但未显示出任何疾病相关性，重测序也未在该人群中鉴定出任何新的常见编码区变异。在该人群中检测的6q23和4q27 SNP是非多态性的，TRAF1/C5、CD40和CCL21 SNP在该韩国患者人群中未显示出与RA相关的任何证据。
白种人和韩国患者的RA遗传危险因素不同。尽管不同种族的患者共享HLA区域作为主要遗传风险基因座，但大多数在白种人中显示与疾病显著相关的其他基因在韩国RA患者中似乎不起作用。
