Rare Copy Number Variants Identified Suggest the Regulating Pathways in Hypertension-Related Left Ventricular...

Area of Science:

• Cardiovascular Genetics
• Genomics
• Hypertension Research

Background:

• Left ventricular hypertrophy (LVH) is a significant risk factor for cardiovascular morbidity and mortality.
• LVH in hypertensive patients has a complex, multifactorial, and polygenic basis.
• The role of rare genetic variations in LVH pathogenesis remains incompletely understood.

Purpose of the Study:

• To investigate the potential contribution of rare copy number variants (CNVs) to the pathogenesis of LVH in hypertensive patients.
• To identify specific CNVs associated with hypertension-related LVH.
• To explore the functional implications of identified CNVs in cardiac development and disease.

Main Methods:

• Genotyping of 258 hypertensive patients, including 95 with LVH, using a high-resolution SNP array.
• Identification and stringent filtering of rare and private CNVs.
• Gene Ontology, pathway, and network enrichment analyses to assess functional relevance.

Main Results:

• 208 rare or private CNVs were identified exclusively in hypertensive patients with LVH.
• Functional analyses confirmed the involvement of genes related to cardiac development and phenotypes.
• Network analyses indicated involvement in transcription factors regulating the "foetal cardiac gene programme" and hypertrophic cascade.

Conclusions:

• Multiple, individually rare CNVs altering specific genes may contribute to the pathogenesis of hypertension-related LVH.
• These findings provide supporting evidence for the impact of rare CNVs on susceptibility to common complex diseases like hypertension-related LVH.
• Rare CNVs represent a potential factor in the lower heritability observed in this condition.