What Can Genetic Studies of Left Ventricular Mass Tell Us?

Abstract

Left ventricular hypertrophy (LVH), whether measured by electrocardiography, echocardiography, or at autopsy, is associated with increased risk of cardiovascular morbidity and mortality.1,2 Although LVH has been associated with several clinical characteristics such as age, sex, body mass index, and hypertension, the effects and their directionality have varied according to the criteria for LVH.3 Aggregation within families suggests a heritable component due to genetics,4 although a recent study of echocardiographic left ventricular mass in a large sample was unable to identify common genetic factors.5 Treatment of hypertensives with LVH can lead to its regression and with it reduction in risk of cardiovascular disease.6 Thus, it appears to be a modifiable risk factor, although LVH induced by exercise training is thought to be benign. Thus, LVH is a complex trait with diverse definitions, has multiple clinical and genetic contributors and is a modifiable risk factor in some but not all settings. Article see p 626 It is not surprising therefore that the (patho-) physiological mechanisms that underlie LVH remain incompletely characterized. Human genetics offers one opportunity to expose mechanisms not previously recognized to play a role in the development of LVH. Shah et al report in this issue of Circulation Cardiovascular Genetics a genetic screen to identify common genetic variants related to electrocardiographic correlates of left ventricular mass (ECG LVM): 2 reflecting simple voltage measures—Sokolow-Lyon voltage and 12-lead QRS voltage sum—and 2 incorporating QRS duration—Cornell product and QRS voltage product.7 The investigators genotyped gene-focused single-nucleotide polymorphisms (SNPs) found on the ITMAT-Broad-CARE (IBC) array, marketed by Illumina as the HumanCVD BeadChip 50K array, with ≈35 000 SNPs passing quality control. The array includes SNPs at 2100 candidate genes selected for being implicated in processes thought to be involved in cardiovascular disease as well as some …