Rare copy number variants identified suggest the regulating pathways in hypertension-related left ventricular hypertrophy

• Main Authors: Basir, F. (Author), Boon-Peng, H. (Author), Danuri, N. (Author), Jusoh, J.A.M (Author), Majid, F. (Author), Marshall, C.R (Author), Scherer, S.W (Author), Thiruvahindrapuram, B. (Author), Yusoff, K. (Author)
• Format: Article
• Language: English
• Published: Public Library of Science 2016
• Subjects: adult; Article; case control study; Case-Control Studies; complication; controlled study; copy number variation; DNA Copy Number Variations; female; Female; gene frequency; Gene Frequency; gene ontology; Gene Ontology; gene regulatory network; Gene Regulatory Networks; genetic association; Genetic Association Studies; genetic association study; genetic predisposition; Genetic Predisposition to Disease; genetic susceptibility; genetic variability; genetics; heart left ventricle hypertrophy; heritability; human; Humans; hypertension; Hypertension; Hypertrophy, Left Ventricular; major clinical study; male; Male; middle aged; Middle Aged; molecular pathology; signal transduction; Signal Transduction
• Online Access: View Fulltext in Publisher; View in Scopus
• ISBN: 19326203 (ISSN)
• ISSN: 19326203 (ISSN)
• DOI: 10.1371/journal.pone.0148755

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality, and a powerful predictor of adverse cardiovascular outcomes in the hypertensive patients. It has complex multifactorial and polygenic basis for its pathogenesis. We hypothesized that rare copy number variants (CNVs) contribute to the LVH pathogenesis in hypertensive patients. Copy number variants (CNV) were identified in 258 hypertensive patients, 95 of whom had LVH, after genotyping with a high resolution SNP array. Following stringent filtering criteria, we identified 208 rare, or private CNVs that were only present in our patients with hypertension related LVH. Preliminary findings from Gene Ontology and pathway analysis of this study confirmed the involvement of the genes known to be functionally involved in cardiac development and phenotypes, in line with previously reported transcriptomic studies. Network enrichment analyses suggested that the gene-set was, directly or indirectly, involved in the transcription factors regulating the "foetal cardiac gene programme" which triggered the hypertrophic cascade, confirming previous reports. These findings suggest that multiple, individually rare copy number variants altering genes may contribute to the pathogenesis of hypertension-related LVH. In summary, we have provided further supporting evidence that rare CNV could potentially impact this common and complex disease susceptibility with lower heritability. © 2016 Boon-Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.