Overlap of disease susceptibility loci for rheumatoid arthritis and juvenile idiopathic arthritis
Overlap of disease susceptibility loci for rheumatoid arthritis and juvenile idiopathic arthritis
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DOI：
10.1136/ard.2009.110650
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发表时间：
2010-06-01
影响因子：
27.4
通讯作者：
Thomson, Wendy
中科院分区：
文献类型：
--
作者：
Hinks, Anne;Eyre, Steve;Thomson, Wendy
背景全基因组关联研究（GWAS）在寻找复杂遗传自身免疫性疾病的易感性危险因素方面取得了巨大成功。随着越来越多的研究发表，这些疾病之间有相当多的基因位点重叠的证据正在出现。在另一种复杂的遗传性自身免疫性疾病幼年特发性关节炎（JIA）中，利用自身免疫性疾病GWAS或候选基因研究的信息来帮助寻找新的JIA易感位点的策略已经成功，并证实与PTPN22和IL2RA两个基因相关。类风湿关节炎（Rheumatoid arthritis， RA）是一种自身免疫性疾病，与JIA具有相似的临床和病理特征，因此最近发现的RA易感位点也是JIA的优秀候选位点。目的探讨类风湿关节炎与JIA疾病易感位点的重叠情况。方法对1054例JIA患者和3531例对照进行基因分型，分析9个ra相关位点的15个单核苷酸多态性（snp）与JIA的相关性。采用PLINK遗传分析软件比较病例与对照组的等位基因频率和基因型频率。结果鉴定出2个JIA易感位点，其中1个为新发现的JIA关联位点（STAT4）， 2个证实了先前发表的与JIA相关的TRAF1/C5位点。JIA与另外3个基因座（Chr6q23、KIF5A和PRKCQ）存在关联的微弱证据，值得进一步研究。结论所有这些位点都是已知JIA发病机制的良好候选位点，因为已知这些区域内的基因（TRAF1、STAT4、TNFAIP3、PRKCQ）参与t细胞受体信号传导或激活途径。
Background Genome-wide association studies (GWAS) have been extremely successful in the search for susceptibility risk factors for complex genetic autoimmune diseases. As more studies are published, evidence is emerging of considerable overlap of loci between these diseases. In juvenile idiopathic arthritis (JIA), another complex genetic autoimmune disease, the strategy of using information from autoimmune disease GWAS or candidate gene studies to help in the search for novel JIA susceptibility loci has been successful, with confirmed association with two genes, PTPN22 and IL2RA. Rheumatoid arthritis (RA) is an autoimmune disease that shares similar clinical and pathological features with JIA and, therefore, recently identified confirmed RA susceptibility loci are also excellent JIA candidate loci.Objective To determine the overlap of disease susceptibility loci for RA and JIA.Methods Fifteen single nucleotide polymorphisms (SNPs) at nine RA-associated loci were genotyped in Caucasian patients with JIA (n = 1054) and controls (n = 3531) and tested for association with JIA. Allele and genotype frequencies were compared between cases and controls using the genetic analysis software, PLINK.Results Two JIA susceptibility loci were identified, one of which was a novel JIA association (STAT4) and the second confirmed previously published associations of the TRAF1/C5 locus with JIA. Weak evidence of association of JIA with three additional loci (Chr6q23, KIF5A and PRKCQ) was also obtained, which warrants further investigation.Conclusion All these loci are good candidates in view of the known pathogenesis of JIA, as genes within these regions (TRAF1, STAT4, TNFAIP3, PRKCQ) are known to be involved in T-cell receptor signalling or activation pathways.