Modifier genes for sudden cardiac death

被引:66
作者
Schwartz, Peter J. [1 ,2 ]
Crotti, Lia [1 ,2 ,3 ,4 ]
George, Alfred L., Jr. [5 ]
机构
[1] IRCCS, Ist Auxol Italiano, Ctr Cardiac Arrhythmias Genet, Via Pier Lombardo 22, I-20135 Milan, Italy
[2] IRCCS, Ist Auxol Italiano, Lab Cardiovasc Genet, Via Pier Lombardo 22, I-20135 Milan, Italy
[3] Univ Milano Bicocca, Dept Med & Surg, Via Cadore 48, I-20900 Monza, Italy
[4] IRCCS, Ist Auxol Italiano, Dept Cardiovasc Neural & Metab Sci, San Luca Hosp, Piazzale Brescia 20, I-20149 Milan, Italy
[5] Northwestern Univ, Dept Pharmacol, Feinberg Sch Med, Searle 8-510,320 East Super St, Chicago, IL 60611 USA
关键词
Genetics; Long QT syndrome; Acute myocardial infarction; Genetic variants; Genetic modifiers; LONG-QT SYNDROME; ACUTE MYOCARDIAL-INFARCTION; 3' UNTRANSLATED REGION; VENTRICULAR-FIBRILLATION; INTERVAL DURATION; COMMON VARIANTS; HEART-RATE; COMPOUND MUTATIONS; DISEASE SEVERITY; NOS1AP GENE;
D O I
10.1093/eurheartj/ehy502
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Genetic conditions, even those associated with identical gene mutations, can present with variable clinical manifestations. One widely accepted explanation for this phenomenon is the existence of genetic factors capable of modifying the consequences of disease-causing mutations (modifier genes). Here, we address the concepts and principles by which genetic factors may be involved in modifying risk for cardiac arrhythmia, then discuss the current knowledge and interpretation of their contribution to clinical heterogeneity. We illustrate these concepts in the context of two important clinical conditions associated with risk for sudden cardiac death including a monogenic disorder (congenital long QT syndrome) in which the impact of modifier genes has been established, and a complex trait (life-threatening arrhythmias in acute myocardial infarction) for which the search for genetic modifiers of arrhythmic risk is more challenging. Advances in understanding the contribution of modifier genes to a higher or lower propensity towards sudden death should improve patient-specific risk stratification and be a major step towards precision medicine.
引用
收藏
页码:3925 / +
页数:10
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