Implications of genome-wide association studies in novel therapeutics in primary biliary cirrhosis.
Implications of genome-wide association studies in novel therapeutics in primary biliary cirrhosis.
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DOI：
10.1002/eji.201344270
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发表时间：
2014-04
影响因子：
5.4
通讯作者：
Invernizzi, Pietro
中科院分区：
文献类型：
--
作者：
Carbone, Marco;Lleo, Ana;Sandford, Richard N.;Invernizzi, Pietro
全基因组关联研究（GWAS）彻底改变了对原发性胆汁性肝硬化（PBC）等复杂疾病的遗传影响的研究。最近的GWAS已经确定了许多疾病相关的遗传变异。总体而言，这些突出了PBC中关键免疫途径的显著贡献，其可能参与耐受性丧失和随后的炎症反应和慢性胆管损伤的初始机制。GWAS的结果有可能转化为生物学知识，并有望转化为临床应用。在GWAS中突出显示了许多免疫途径，这些免疫途径可能在PBC和其他自身免疫性疾病中具有治疗意义，例如抗白细胞介素-12/白细胞介素-23、核因子-kb、肿瘤坏死因子、磷脂酰肌醇信号传导和hedgehog信号传导途径。GWAS的发现正在导致PBC或其他自身免疫性疾病的临床应用的其他领域包括疾病分类，风险预测和药物开发。在这篇综述中，我们概述了可能的下一步，可能有助于加快从遗传学研究的生物学知识，将指导发展预测，预防或治疗措施，在PBC的进展。
Genome-wide association studies (GWAS) have revolutionized the search for genetic influences on complex disorders, such as primary biliary cirrhosis (PBC). Recent GWAS have identified many disease-associated genetic variants. These, overall, highlighted the remarkable contribution of key immunological pathways in PBC that may be involved in the initial mechanisms of loss of tolerance and the subsequent inflammatory response and chronic bile duct damage. Results from GWAS have the potential to be translated in biological knowledge and, hopefully, clinical application. There are a number of immune pathways highlighted in GWAS that may have therapeutic implications in PBC and in other autoimmune diseases, such as the anti-interleukin-12/interleukin-23, nuclear factor-kb, tumor necrosis factor, phosphatidylinositol signaling and hedgehog signaling pathways. Further areas in which GWAS findings are leading to clinical applications either in PBC or in other autoimmune conditions, include disease classification, risk prediction and drug development. In this review we outline the possible next steps that may help accelerate progress from genetic studies to the biological knowledge that would guide the development of predictive, preventive, or therapeutic measures in PBC.
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影响因子：
13.5
作者：
Dhirapong, Amy;Yang, Guo-Xiang;Nadler, Steven;Zhang, Weici;Tsuneyama, Koichi;Leung, Patrick;Knechtle, Stuart;Ansari, Aftab A.;Coppel, Ross L.;Liu, Fu-Tong;He, Xiao-Song;Gershwin, M. Eric
通讯作者：
Gershwin, M. Eric
影响因子：
13.5
作者：
Ando, Yugo;Yang, Guo-Xiang;Tsuda, Masanobu;Kawata, Kazuhito;Zhang, Weici;Nakajima, Takahiko;Tsuneyama, Koichi;Leung, Patrick;Lian, Zhe-Xiong;Okazaki, Kazuichi;Ridgway, William M.;Norman, Gary L.;Ansari, Aftab A.;He, Xiao-Song;Coppel, Ross L.;Gershwin, M. Eric
通讯作者：
Gershwin, M. Eric
影响因子：
56.9
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
通讯作者：
Cho, Judy H.
影响因子：
158.5
作者：
Genovese, MC;Becker, J;Dougados, M
通讯作者：
Dougados, M
DOI：
10.1073/pnas.0903103106
发表时间：
2009-06-09
影响因子：
11.1
作者：
Hindorff, Lucia A.;Sethupathy, Praveen;Manolio, Teri A.
通讯作者：
Manolio, Teri A.