Rheumatoid arthritis genetics: 2009 update.
Rheumatoid arthritis genetics: 2009 update.
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DOI：
10.1007/s11926-009-0050-0
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发表时间：
2009-10-01
影响因子：
5
通讯作者：
Plenge, Robert M
中科院分区：
文献类型：
--
作者：
Plenge, Robert M
最近的人类基因发现增加了我们对类风湿性关节炎(RA)易感性的了解。全基因组关联研究已将已证实的RA风险基因座的数量扩大到人类白细胞抗原-DRB1“共享表位”等位基因之外，包括额外的主要组织相容性复合体(MHC)风险等位基因和MHC以外的10多个区域。新发现的风险等位基因在普通人群中很常见，对类风湿性关节炎风险的影响不大，加在一起解释的疾病风险差异不到5%。虽然大多数基因座的实际因果突变和因果基因仍未确定，但这些研究已经开始揭示出普遍的主题：许多风险基因与其他自身免疫性疾病相关；许多基因属于离散的生物学途径(例如，核因子kappa轻链增强子激活的B细胞信号通路)；人类遗传学可以将疾病分组为具有临床意义的亚集类别(例如，是否存在自身抗体)。这篇综述讨论了最近的类风湿性关节炎基因发现在改善患者护理方面的潜力。
Recent human genetic discoveries have increased our understanding of rheumatoid arthritis (RA) susceptibility. Genome-wide association studies have expanded the number of validated RA risk loci beyond HLA-DRB1 "shared epitope" alleles to include additional major histocompatibility complex (MHC) risk alleles and more than 10 regions outside the MHC. The newly discovered risk alleles are common in the general population, have a modest effect on RA risk, and together explain less than 5% of the variance in disease risk. Whereas the actual causal mutation and causal gene for most loci remain to be determined, these studies are beginning to reveal general themes: many risk loci are associated with other autoimmune diseases; many genes fall within discrete biological pathways (eg, the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway); and human genetics can group diseases into clinically meaningful subset categories (eg, presence or absence of autoantibodies). This review discusses recent RA genetic discoveries in terms of their potential to improve patient care.