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

• Published in: PLoS ONE
• Main Author: Boon-Peng H.; Jusoh J.A.M.; Marshall C.R.; Majid F.; Danuri N.; Basir F.; Thiruvahindrapuram B.; Scherer S.W.; Yusoff K.
• Format: Article
• Language: English
• Published: Public Library of Science 2016
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84961141346&doi=10.1371%2fjournal.pone.0148755&partnerID=40&md5=e199462e8e5aeed7970e25a2e95a7d8e

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.