Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy.
Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy.
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DOI：
10.1016/j.hrthm.2011.10.016
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发表时间：
2012-03
期刊：
影响因子：
5.5
通讯作者：
Ellinor PT
中科院分区：
文献类型：
--
作者：
Refaat MM;Lubitz SA;Makino S;Islam Z;Frangiskakis JM;Mehdi H;Gutmann R;Zhang ML;Bloom HL;MacRae CA;Dudley SC;Shalaby AA;Weiss R;McNamara DM;London B;Ellinor PT
扩张型心肌病（DCM）是心力衰竭和死亡的主要原因。DCM的病因是遗传异质性的。我们试图确定RNA剪接蛋白RBM 20突变的流行率，在一个大的DCM队列中，并确定RBM 20的遗传变异是否与临床结果相关。GRADE（除颤器事件的遗传风险评估）研究中纳入的受试者年龄至少为18岁，射血分数≤ 30%，植入了心律转复除颤器（ICD）。在DCM受试者中筛选RBM 20的编码区和剪接点;在所有GRADE受试者中对RBM 20的两种常见多态性rs 942077和rs35141404进行基因分型。1465例受试者入组GRADE研究，283例DCM受试者接受RBM 20突变筛查。DCM受试者的平均年龄为58 ± 13岁，64%为男性，植入ICD后的平均随访时间为24.2 ± 17.1个月。在8例DCM受试者中发现了RBM 20突变（2.8%）。突变携带者的生存率、移植率和ICD治疗频率与非突变携带者相似。8例RBM 20突变受试者中有3例（37.5%）患有房颤（AF），而19例（7.4%）无突变受试者患有AF（p= 0.02）。在所有GRADE受试者中，rs35141404与AF相关（次要等位基因OR 0.62，95% CI 0.44-0.86，p=0.006）。在患有DCM的GRADE受试者亚组中，rs35141404与AF相关（次要等位基因OR 0.58，p=0.047）。在约3%的DCM受试者中观察到RBM 20突变。突变携带者的存活率、移植率和ICD治疗频率没有差异。
Dilated cardiomyopathy (DCM) is a leading cause of heart failure and death. The etiology of DCM is genetically heterogeneous. We sought to define the prevalence of mutations in the RNA splicing protein, RBM20, in a large cohort with DCM, and to determine if genetic variation in RBM20 is associated with clinical outcomes. Subjects included in the GRADE (Genetic Risk Assessment of Defibrillator Events) study were at least 18 years of age, had an ejection fraction of ≤ 30%, and an implantable cardioverter-defibrillator (ICD). The coding region and splice junctions of RBM20 were screened in DCM subjects; two common polymorphisms in RBM20, rs942077 and rs35141404, were genotyped in all GRADE subjects. 1465 subjects were enrolled in the GRADE study and 283 with DCM were screened for RBM20 mutations. The mean age of subjects with DCM was 58 ± 13 years, 64% were male and the mean follow up was 24.2 ± 17.1 months after ICD placement. RBM20 mutations were identified in eight subjects with DCM (2.8%). Mutation carriers had a similar survival, transplantation rate, and frequency of ICD therapy compared to non-mutation carriers. Three of eight subjects (37.5%) with RBM20 mutations had atrial fibrillation (AF) whereas 19 (7.4%) subjects without mutations had AF (p= 0.02). Among all GRADE subjects, rs35141404 was associated with AF (minor allele OR 0.62, 95% CI 0.44–0.86, p=0.006). In the subset of GRADE subjects with DCM, rs35141404 was associated with AF (minor allele OR 0.58, p=0.047). Mutations in RBM20 were observed in approximately 3% of subjects with DCM. There were no differences in survival, transplantation rate, and frequency of ICD therapy in mutation carriers.
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影响因子：
2.8
作者：
Michels, VV;Olson, TM;Driscoll, DJ
通讯作者：
Driscoll, DJ
影响因子：
37.8
作者：
CODD, MB;SUGRUE, DD;MELTON, LJ
通讯作者：
MELTON, LJ
影响因子：
2.1
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Bloom HL;Shukrullah I;Veledar E;Gutmann R;London B;Dudley SC
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Dudley SC
影响因子：
10.8
作者：
Duboscq-Bidot, Laetitia;Xu, Peng;Villard, Eric
通讯作者：
Villard, Eric
影响因子：
2.8
作者：
FUSTER, V;GERSH, BJ;FRYE, RL
通讯作者：
FRYE, RL