Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
Heart Rhythm. 2012 Mar;9(3):390-6. doi: 10.1016/j.hrthm.2011.10.016. Epub 2011 Oct 17.
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 whether genetic variation in RBM20 is associated with clinical outcomes.
Subjects included in the Genetic Risk Assessment of Defibrillator Events (GRADE) study were aged at least 18 years, had an ejection fraction of ≤30%, and an implantable cardioverter-defibrillator (ICD). The coding region and splice junctions of RBM20 were screened in subjects with DCM; 2 common polymorphisms in RBM20, rs942077 and rs35141404, were genotyped in all GRADE subjects.
A total of 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 males, and the mean follow-up time was 24.2 ± 17.1 months after ICD placement. RBM20 mutations were identified in 8 subjects with DCM (2.8%). Mutation carriers had a similar survival, transplantation rate, and frequency of ICD therapy compared with nonmutation carriers. Three of 8 subjects with RBM20 mutations (37.5%) had atrial fibrillation (AF), whereas 19 subjects without mutations (7.4%) had AF (P = .02). Among all GRADE subjects, rs35141404 was associated with AF (minor allele odds ratio = 0.62; 95% confidence interval = 0.44-0.86; P = .006). In the subset of GRADE subjects with DCM, rs35141404 was associated with AF (minor allele odds ratio = 0.58; P = .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.
扩张型心肌病（DCM）是心力衰竭和死亡的主要原因。DCM 的病因具有遗传异质性。
我们旨在确定在患有 DCM 的大样本中 RNA 剪接蛋白 RBM20 突变的流行率，并确定 RBM20 中的遗传变异是否与临床结局相关。
入选 Genetic Risk Assessment of Defibrillator Events（GRADE）研究的受试者年龄至少 18 岁，射血分数≤30%，并植入了植入式心律转复除颤器（ICD）。对 DCM 患者进行 RBM20 的编码区和剪接位点筛查；对所有 GRADE 受试者进行 RBM20 两个常见多态性 rs942077 和 rs35141404 的基因分型。
共有 1465 名受试者入组 GRADE 研究，对 283 名 DCM 患者进行了 RBM20 突变筛查。DCM 患者的平均年龄为 58±13 岁，64%为男性，ICD 植入后平均随访时间为 24.2±17.1 个月。在 8 名 DCM 患者中发现了 RBM20 突变（2.8%）。突变携带者与非突变携带者的生存率、移植率和 ICD 治疗频率相似。8 名携带 RBM20 突变的患者中有 3 名（37.5%）患有房颤（AF），而 19 名无突变的患者中有 19 名（7.4%）患有房颤（P=0.02）。在所有 GRADE 受试者中，rs35141404 与房颤相关（次要等位基因比值比=0.62；95%置信区间=0.44-0.86；P=0.006）。在 GRADE 患者亚组中，rs35141404 与房颤相关（次要等位基因比值比=0.58；P=0.047）。
在 DCM 患者中，约 3%的患者存在 RBM20 突变。突变携带者的生存率、移植率和 ICD 治疗频率无差异。
