Genetics of rheumatoid arthritis - a comprehensive review.
Genetics of rheumatoid arthritis - a comprehensive review.
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DOI：
10.1007/s12016-012-8346-7
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发表时间：
2013-10
影响因子：
9.1
通讯作者：
Szekanecz, Zoltan
中科院分区：
文献类型：
--
作者：
Kurko, Julia;Besenyei, Timea;Laki, Judit;Glant, Tibor T.;Mikecz, Katalin;Szekanecz, Zoltan
关键词：
遗传、环境和自身免疫的“百慕大三角”参与类风湿关节炎（RA）的发病机制。本文综述了遗传因素对类风湿关节炎的病因、发病机制和预后的影响。据估计，RA的遗传率约为60%，而HLA对遗传率的贡献约为11 - 37%。除了已知的共享表位（shared epitope， SE）等位基因如HLA-DRB1*01和DRB1*04外，其他HLA等位基因如HLA-DRB1*13和DRB1*15与RA易感性相关。一种新的SE分类方法将SE等位基因分为S1、S2、S3P和S3D组，其中主要是S2和S3P组与血清阳性RA易感性相关。与RA最相关的非hla基因单核苷酸多态性（snp）包括PTPN22、IL23R、TRAF1、CTLA4、IRF5、STAT4、CCR6、PADI4。大型全基因组关联研究（GWAS）已经确定了30多个与RA发病有关的基因座。HLA和一些非HLA基因可以区分抗瓜氨酸蛋白抗体（ACPA）血清阳性和血清阴性RA。遗传易感性也与环境因素有关，主要是吸烟。在啮齿动物关节炎模型中进行的一些GWAS研究证实了人类基因的作用。例如，在胶原诱导（CIA）和蛋白多糖诱导的关节炎（PgIA）模型中，已经鉴定出两个重要的基因座- Pgia26/Cia5和Pgia2/Cia2/Cia3，分别对应人类PTPN22/CD2和TRAF1/C5基因座。最后，药物基因组学确定了snp或多种遗传特征，这些特征可能与对传统疾病改善药物和生物制剂的反应有关。
The “Bermuda triangle” of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11–37 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci — Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively — have been identified. Finally, pharmacogenomics identified SNPs or multiple genetic signatures that may be associated with responses to traditional disease-modifying drugs and biologics.
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影响因子：
--
作者：
Ding, Bo;Padyukov, Leonid;Lundstrom, Emeli;Seielstad, Mark;Plenge, Robert M.;Oksenberg, Jorge R.;Gregersen, Peter K.;Alfredsson, Lars;Klareskog, Lars
通讯作者：
Klareskog, Lars
影响因子：
4.9
作者：
Adarichev, VA;Vermes, C;Glant, TT
通讯作者：
Glant, TT
DOI：
10.1038/ncprheum0072
发表时间：
2006-01-01
期刊：
NATURE CLINICAL PRACTICE RHEUMATOLOGY
影响因子：
--
作者：
Cronstein, BN
通讯作者：
Cronstein, BN
影响因子：
2.1
作者：
Danila MI;Hughes LB;Bridges SL
通讯作者：
Bridges SL
影响因子：
4.9
作者：
Ahlqvist E;Hultqvist M;Holmdahl R
通讯作者：
Holmdahl R