肥厚型心肌病基因型-表型关联研究进展

Research progress of the correlation between genotype and phenotype in hypertrophic cardiomyopathy

肥厚型心肌病(hypertrophic cardiomyopathy,HCM)是一种以左心室肥厚为突出特征的常染色体显性遗传病,其发病率为1/500~1/200。目前已发现超过30个基因的1500种突变与该疾病的发生发展相关,致病基因变异连同修饰基因多态性、环境因素等影响因素发挥作用,使得疾病表型极具异质性,临床表现上从无任何症状到心源性猝死均可发生,病理表型主要包括心肌细胞肥大、排列紊乱及纤维化、心肌缺血等。近年来,许多研究致力于探究HCM基因型对表型的影响,并基于遗传背景对HCM的治疗方法进行研发。本文以HCM基因型–表型的关联为重点,从HCM的致病基因、关联影响因素和最新治疗手段等多方面综述了HCM的研究进展,以期为研究HCM的发生发展及治疗方向提供遗传学方面的思路。

Hypertrophic cardiomyopathy(HCM)is an autosomal dominant genetic disease characterized by left ventricular hypertrophy with prevalence of 1/500–1/200.Up to now,1500 mutations in more than 30 genes have been found to be related to the disease.Pathogenic gene mutations together with polymorphisms of modifying genes and environmental factors play various roles in the disease processes,resulting in phenotypic heterogeneity of the disease,ranging from no symptoms to sudden cardiac death.The pathological phenotypes of HCM mainly include cardiomyocyte hypertrophy,disordered array,fibrosis,myocardial ischemia,and others.In recent years,many research efforts have been devoted to exploring the influence of HCM genotype on phenotype,and development of treatment methods based on genetics.This article focuses on the correction between HCM genotype and phenotype and summarizes the research progresses on HCM in terms of pathogenic genes,pathogenesis,associated modification factors and treatment methods,thereby providing insights on the future research and development on the genetics of HCM.