Genetics of rheumatoid arthritis.
Genetics of rheumatoid arthritis.
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DOI：
10.1007/s00281-022-00912-0
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发表时间：
2022-01
影响因子：
9
通讯作者：
Padyukov L
中科院分区：
文献类型：
--
作者：
Padyukov L
类风湿性关节炎（RA）是一种累及对称关节的炎症性自身免疫性疾病，通常以持续性疼痛、压痛和关节破坏为特征。绝大多数 RA 患者都会产生自身抗体，并且免疫细胞参与疾病发展已得到广泛认可，滑膜组织中其他类型细胞（如成纤维细胞）的贡献也是如此。众所周知，HLA 基因座存在主要的遗传关联，而多个非 HLA 遗传变异显示 RA 风险相对较低。 HLA 和非 HLA 关联都表明，自身抗体阳性与自身抗体阴性 RA 的遗传关联特征是不同的。 HLA-DRB1 的多个等位基因与自身抗体阳性 RA 的高风险相关，其中蛋白质序列 11 位缬氨酸（HLA-DRB1*04 和 *10 等位基因）的风险最高。对于与 HLA-DRB1*13 等位基因相关的自身抗体阳性 RA 风险有很强的保护作用。尽管主要的遗传关联已为人所知数年，但对这些变异导致 RA 风险增加的具体机制的了解仍在进行中。目前的研究重点是参与 T 细胞激活过程中推定肽识别的免疫受体的结合，以及细胞信号传导机制的研究。至少部分 RA 风险可以通过基因与基因以及基因与环境的相互作用来解释。目前有超过 150 个具有多态性的候选位点与 RA 相关，主要与血清阳性疾病有关，预计未来通过对不同人群的调查会有新的发现。这项新研究将有助于为 RA 研究中遗传、表观遗传、转录组和蛋白质组数据的持续整合奠定坚实的基础。
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease involving symmetric joints and is generally characterized by persistent pain, tenderness, and destruction of joints. The vast majority of RA patients produce autoantibodies, and immune cell involvement in disease development is well recognized, as is the contribution of other types of cells in synovial tissue, like fibroblasts. It is known that there are major genetic associations with the HLA locus, while multiple non-HLA genetic variants display relatively low risk of RA. Both HLA and non-HLA associations suggest that the profiles of genetic associations for autoantibody-positive vs. autoantibody-negative RA are different. Several alleles of HLA-DRB1 are associated with high risk for autoantibody-positive RA, with the strongest risk characterized by valine at position 11 of the protein sequence (HLA-DRB1*04 and *10 alleles). There is a strong protective effect for the risk of autoantibody-positive RA associated with HLA-DRB1*13 alleles. Although major genetic associations have been known for several years, understanding of the specific mechanisms in the development of increased risk of RA for these variations is work in progress. Current studies focus on the binding of immune receptors involved in recognition of putative peptides in activation of T cells, as well as investigation of cell signaling mechanisms. At least a part of RA risk could be explained by gene–gene and gene-environment interactions. There are currently more than 150 candidate loci with polymorphisms that associate with RA, mainly related to seropositive disease, and new discoveries are anticipated in the future from investigation of diverse human populations. This new research will help create a strong foundation for the continuing process of integrating genetic, epigenetic, transcriptomic, and proteomic data in studies of RA.
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影响因子：
--
作者：
Keenan, Brendan T.;Chibnik, Lori B.;Cui, Jing;Ding, Bo;Padyukov, Leonid;Kallberg, Henrik;Bengtsson, Camilla;Klareskog, Lars;Alfredsson, Lars;Karlson, Elizabeth W.
通讯作者：
Karlson, Elizabeth W.
影响因子：
13.3
作者：
Cribbs, Adam P.;Kennedy, Alan;Williams, Richard O.
通讯作者：
Williams, Richard O.
影响因子：
9.8
作者：
Han, Buhm;Diogo, Dorothee;Raychaudhuri, Soumya
通讯作者：
Raychaudhuri, Soumya
影响因子：
12.3
作者：
Gomez-Cabrero D;Almgren M;Sjöholm LK;Hensvold AH;Ringh MV;Tryggvadottir R;Kere J;Scheynius A;Acevedo N;Reinius L;Taub MA;Montano C;Aryee MJ;Feinberg JI;Feinberg AP;Tegnér J;Klareskog L;Catrina AI;Ekström TJ
通讯作者：
Ekström TJ
影响因子：
27.4
作者：
Ha E;Bae SC;Kim K
通讯作者：
Kim K