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NEJM:单核苷酸多态性或可帮助预测双极性情感障碍患者对锂疗法的反应

  1. NEJM
  2. 单核苷酸多态性
  3. 双极性情感障碍
  4. 患者
  5. 锂疗法

来源:生物谷 2014-01-05 23:06

来自台北生物医学科学研究所的研究人员通过研究表示,对于第一型双极性情感障碍 (bipolar I disorder)患者来讲,谷氨酸脱羧酶样蛋白1(GADL1)中两个单一的单核苷酸多态性(SNPs)就可以预测患者对锂疗法的反应。

2014年1月6日 讯 /生物谷BIOON/ --近日,刊登在国际著名杂志New England Journal of Medicine上的一篇研究报告中,来自台北生物医学科学研究所的研究人员通过研究表示,对于第一型双极性情感障碍 (bipolar I disorder)患者来讲,谷氨酸脱羧酶样蛋白1(GADL1)中两个单一的单核苷酸多态性(SNPs)就可以预测患者对锂疗法的反应。

许多患双极神经元障碍的患者对锂疗法并不会有反应,研究人员在文章中对患有第一型双极性情感障碍的1761名汉族人进行研究来评估其对锂疗法的反应;随后研究者对患有第一型双极性情感障碍且接受锂疗法的294名患者组成的亚群进行全基因组关联性研究,结果显示SNPs和100名患者的样品存在强烈相关性,而且也和随后的24名患者的样品存在关联,而对94名患者进行GADL1测序发现或者对锂疗法有反应,而另外94名被测序患者病没有反应。

研究者表示,通过全基因组关联性研究发现了两个位点rs17026688和rs17026651与患者对锂疗法是否有反应存在最密切的关系。

研究者表示,预测患者对锂疗法反应的敏感性在两个SNPs中占到了93%的比例,而且其也可以帮助区分患者的反应好坏程度。这项研究中研究者揭示了GADL1的遗传突变和第一型双极性情感障碍的汉族人对锂疗法的反应直接相关。(生物谷Bioon.com)

Variant GADL1 and Response to Lithium Therapy in Bipolar I Disorder

Chien-Hsiun Chen, Ph.D., Chau-Shoun Lee, M.D., Ph.D., Ming-Ta Michael Lee, Ph.D., Wen-Chen Ouyang, M.D., Ph.D., Chiao-Chicy Chen, M.D., Ph.D., Mian-Yoon Chong, M.D., Ph.D., Jer-Yuarn Wu, Ph.D., Happy Kuy-Lok Tan, M.D., Yi-Ching Lee, Ph.D., Liang-Jen Chuo, M.D., Nan-Ying Chiu, M.D., Hin-Yeung Tsang, M.D., Ph.D., Ta-Jen Chang, M.D., For-Wey Lung, M.D., Sc.D., Chen-Huan Chiu, M.D., Ph.D., Cheng-Ho Chang, M.D., M.Sc., Ying-Sheue Chen, M.D., Yuh-Ming Hou, M.D., Cheng-Chung Chen, M.D., Ph.D., Te-Jen Lai, M.D., Ph.D., Chun-Liang Tung, M.D., Chung-Ying Chen, M.D., Hsien-Yuan Lane, M.D., Ph.D., Tung-Ping Su, M.D., Jung Feng, M.D., Jin-Jia Lin, M.D., Ching-Jui Chang, M.D., Po-Ren Teng, M.D., Chia-Yih Liu, M.D., Chih-Ken Chen, M.D., Ph.D., I-Chao Liu, M.D., D.Sc., Jiahn-Jyh Chen, M.D., Ti Lu, M.D., Chun-Chieh Fan, M.D., Ching-Kuan Wu, M.D., Chang-Fang Li, B.S., Kathy Hsiao-Tsz Wang, M.Sc., Lawrence Shih-Hsin Wu, Ph.D., Hsin-Ling Peng, M.Sc., Chun-Ping Chang, M.Sc., Liang-Suei Lu, M.Sc., Yuan-Tsong Chen, M.D., Ph.D., and Andrew Tai-Ann Cheng, M.D., Ph.D., D.Sc. for the Taiwan Bipolar Consortium

BACKGROUND Lithium has been a first-line choice for maintenance treatment of bipolar disorders to prevent relapse of mania and depression, but many patients do not have a response to lithium treatment. METHODS We selected subgroups from a sample of 1761 patients of Han Chinese descent with bipolar I disorder who were recruited by the Taiwan Bipolar Consortium. We assessed their response to lithium treatment using the Alda scale and performed a genomewide association study on samples from one subgroup of 294 patients with bipolar I disorder who were receiving lithium treatment. We then tested the single-nucleotide polymorphisms (SNPs) that showed the strongest association with a response to lithium for association in a replication sample of 100 patients and tested them further in a follow-up sample of 24 patients. We sequenced the exons, exon–intron boundaries, and part of the promoter of the gene encoding glutamate decarboxylase–like protein 1 (GADL1) in 94 patients who had a response to lithium and in 94 patients who did not have a response in the genomewide association sample. RESULTS Two SNPs in high linkage disequilibrium, rs17026688 and rs17026651, that are located in the introns of GADL1 showed the strongest associations in the genomewide association study (P=5.50×10−37 and P=2.52×10−37, respectively) and in the replication sample of 100 patients (P=9.19×10−15 for each SNP). These two SNPs had a sensitivity of 93% for predicting a response to lithium and differentiated between patients with a good response and those with a poor response in the follow-up cohort. Resequencing of GADL1 revealed a novel variant, IVS8+48delG, which lies in intron 8 of the gene, is in complete linkage disequilibrium with rs17026688 and is predicted to affect splicing. CONCLUSIONS Genetic variations in GADL1 are associated with the response to lithium maintenance treatment for bipolar I disorder in patients of Han Chinese descent. (Funded by Academia Sinica and others.)

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