title: Rare Copy Number Variants Identified Suggest the Regulating Pathways in Hypertension-Related Left Ventricular Hypertrophy.
abstract: 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.
authors.affiliation: Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.|UCSI University, Jalan Menara Gading, UCSI Heights, 56000 Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia.
authors.forename: Hoh
authors.initials: H
authors.lastname: Boon-Peng
authors.affiliation: Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors.forename: Julia Ashazila
authors.initials: JA
authors.lastname: Mat Jusoh
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.|McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Canada.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors.forename: Fadhlina
authors.initials: F
authors.lastname: Majid
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors.forename: Norlaila
authors.initials: N
authors.lastname: Danuri
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000 Sungai Buloh, Selangor, Malaysia.
authors.forename: Fashieha
authors.initials: F
authors.lastname: Basir
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Bhooma
authors.initials: B
authors.lastname: Thiruvahindrapuram
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.|McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Canada.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.affiliation: UCSI University, Jalan Menara Gading, UCSI Heights, 56000 Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia.
authors.forename: Khalid
authors.initials: K
authors.lastname: Yusoff
mesh_terms: D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D005260:Female; D005787:Gene Frequency; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction