Abstract
Left ventricular hypertrophy (LVH) represents a common final pathway leading to heart failure. We have searched for genetic determinants of left ventricular (LV) mass using values for absolute electrocardiographic QRS voltage in a healthy Japanese population. After adjusting for covariates, the corrected S and R wave voltages in leads V1 and V5 from 2,994 healthy volunteers in the Japan Pharmacogenomics Data Science Consortium (JPDSC) database were subjected to a genome-wide association study. Potential associations were validated by an in silico replication study using an independent Japanese population obtained from the Nagahama Prospective Genome Cohort for Comprehensive Human Bioscience. We identified a novel association between the lead V5, R wave voltage in Japanese individuals and SNP rs7301743[G], which maps near the gene encoding T-box transcription factor Tbx3. Meta-analysis of two independent Japanese datasets demonstrated a marginally significant association of SNP rs7301743 in TBX3|MED13L with a 0.071 mV (95% CI, 0.038–0.11 mV) shorter R wave amplitude in the V5 lead per minor allele copy (P = 7.635 x 10−8). The transcriptional repressor, TBX3, is proposed to suppress the development of working ventricular myocardium. Our findings suggest that genetic variation of Tbx3 is associated with LV mass in a healthy Japanese population.
Highlights
Left ventricular hypertrophy (LVH) represents a common final pathway leading to heart failure [1], and is associated with an increased vulnerability to sudden death and acute myocardial infarction [2]
Age, log-transformed body mass index (BMI), log heart rate (HR), systolic pressure, diastolic pressure, serum potassium, serum calcium, and Japanese geographic region should be included as covariates
single-nucleotide polymorphisms (SNPs) associated with R wave in V5 (RV5) and S wave in V1 (SV1) were not the same
Summary
Left ventricular hypertrophy (LVH) represents a common final pathway leading to heart failure [1], and is associated with an increased vulnerability to sudden death and acute myocardial infarction [2]. Left ventricular (LV) mass can be regarded as a quantitative trait that is affected by both environmental and genetic factors that vary considerably between individuals. The search for genes conferring an individual's genetic susceptibility to LVH is clinically relevant. Epidemiological research has demonstrated that electrocardiographically diagnosed LVH (ECG-LVH) carries significant prognostic value [4]. Consistent with this, recent genome-wide association studies (GWAS) and genome-wide linkage analysis have shown that ECG-LVH provides unique information about the genetic determinants of LVH [5] [6] [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
