Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: evidence for additional functions of EYS.
Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: evidence for additional functions of EYS.
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DOI：
10.1002/mus.22115
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发表时间：
2011-10
期刊：
影响因子：
3.4
通讯作者：
Vladutiu, Georgirene D.
中科院分区：
文献类型：
--
作者：
Isackson, Paul J.;Ochs-Balcom, Heather M.;Ma, Changxing;Harley, John B.;Peltier, Wendy;Tarnopolsky, Mark;Sripathi, Naganand;Wortmann, Robert L.;Simmons, Zachary;Wilson, Jon D.;Smith, Stephen A.;Barboi, Alexandru;Fine, Edward;Baer, Alan;Baker, Steven;Kaufman, Kenneth;Cobb, Beth;Kilpatrick, Jeffrey R.;Vladutiu, Georgirene D.
在美国接受他汀类药物治疗的近3800万人中，有0.1-0.5%的人经历了严重或危及生命的肌病副作用。我们对严重他汀类肌病患者与他汀类药物耐受组进行了全基因组关联研究（GWAS），以确定遗传易感性位点。在重度他汀类肌病（n=190）和他汀类耐受对照（n=130）的独立组中进行的复制研究导致在6号染色体上的闭眼同源物（EYS）中鉴定出三个SNP，rs 9342288、rs 1337512和rs3857532，提示与重度他汀类肌病的风险相关（p=0.0003-0.0008）。EYS cDNA的分析表明，EYS基因产物是复杂的，并在脊髓以及在视网膜中表达相对丰富。这些EYS基因产物的Notch信号通路的成员和聚集蛋白的结构相似性表明在骨骼肌的结构完整性的维持和再生中可能发挥功能作用。
Of nearly 38 million people in the U.S. receiving statin therapy, 0.1–0.5% experience severe or life-threatening myopathic side effects. We performed a genome-wide association study (GWAS) in patients with severe statin myopathy versus a statin-tolerant group to identify genetic susceptibility loci. Replication studies in independent groups of severe statin myopathy (n=190) and statintolerant controls (n=130) resulted in the identification of three SNPs, rs9342288, rs1337512 and rs3857532, in the eyes shut homolog (EYS) on chromosome 6 suggestive of an association with risk for severe statin myopathy (p=0.0003–0.0008). Analysis of EYS cDNA demonstrated that EYS gene products are complex and expressed with relative abundance in the spinal cord as well as in the retina. Structural similarities of these EYS gene products to members of the Notch signaling pathway and to agrin suggest a possible functional role in the maintenance and regeneration of the structural integrity of skeletal muscle.
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DOI：
10.1073/pnas.87.22.8931
发表时间：
1990-11-01
影响因子：
11.1
作者：
FOLKERS, K;LANGSJOEN, P;TAMAGAWA, H
通讯作者：
TAMAGAWA, H
影响因子：
30.8
作者：
Li, LH;Krantz, ID;Spinner, NB
通讯作者：
Spinner, NB
影响因子：
64.8
作者：
Garg, V;Muth, AN;Srivastava, D
通讯作者：
Srivastava, D
影响因子：
11.4
作者：
Grishkovskaya, I;Avvakumov, GV;Muller, YA
通讯作者：
Muller, YA
影响因子：
2
作者：
Gauderman, WJ
通讯作者：
Gauderman, WJ