肥厚性心肌病
医学
错义突变
候选基因
优势比
外显子组测序
危险系数
心源性猝死
遗传学
内科学
心脏病学
基因
突变
生物
置信区间
作者
Guixin Wu,Jieyun Ruan,Jie Liu,Channa Zhang,Lianming Kang,Jizheng Wang,Yubao Zou,Lingyun Song
标识
DOI:10.1161/jaha.120.018236
摘要
Background The FHOD3 (formin homology 2 domain-containing 3) gene has recently been identified as a causative gene of hypertrophic cardiomyopathy (HCM). However, the pathogenicity of FHOD3 variants remains to be evaluated. This study analyzed the spectrum of FHOD3 variants in a large HCM and control cohort, and explored its correlation with the disease. Methods and Results The genetic analysis of FHOD3 was performed using the whole exome sequencing data from 1000 patients with HCM and 761 controls without HCM. A total of 37 FHOD3 candidate variants were identified, including 25 missense variants and 2 truncating variants. In detail, there were 27 candidate variants detected in 33 (3.3%) patients with HCM, which was significantly higher than in the 12 controls (3.3% versus 1.6%; odds ratio, 2.13; P<0.05). On the basis of familial segregation, we identified one truncating variant (c.1286+2delT) as a causal variant in 4 patients. Furthermore, the FHOD3 candidate variant experienced significantly more risk of cardiovascular death and all-cause death (adjusted hazard ratio [HR], 3.71; 95%, 1.32-8.59; P=0.016; and adjusted HR, 3.02; 95% CI, 1.09-6.85; P=0.035, respectively). Conclusions Our study suggests that FHOD3 is a causal gene for HCM, and that the presence of FHOD3 candidate variants is an independent risk for cardiovascular death and all-cause death in HCM.
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