Institute for Health, Health Care Policy and Aging Research, Rutgers University, 112 Paterson Street, New Brunswick, NJ, 08901, USA.
Pat and Jim Calhoun Cardiology Center, UConn Health, 263 Farmington Ave, Farmington, CT, USA.
Sci Rep. 2023 Oct 5;13(1):16769. doi: 10.1038/s41598-023-44127-1.
Cardiovascular disease (CVD) is caused by a multitude of complex and largely heritable conditions. Identifying key genes and understanding their susceptibility to CVD in the human genome can assist in early diagnosis and personalized treatment of the relevant patients. Heart failure (HF) is among those CVD phenotypes that has a high rate of mortality. In this study, we investigated genes primarily associated with HF and other CVDs. Achieving the goals of this study, we built a cohort of thirty-five consented patients, and sequenced their serum-based samples. We have generated and processed whole genome sequence (WGS) data, and performed functional mutation, splice, variant distribution, and divergence analysis to understand the relationships between each mutation type and its impact. Our variant and prevalence analysis found FLNA, CST3, LGALS3, and HBA1 linked to many enrichment pathways. Functional mutation analysis uncovered ACE, MME, LGALS3, NR3C2, PIK3C2A, CALD1, TEK, and TRPV1 to be notable and potentially significant genes. We discovered intron, 5' Flank, 3' UTR, and 3' Flank mutations to be the most common among HF and other CVD genes. Missense mutations were less common among HF and other CVD genes but had more of a functional impact. We reported HBA1, FADD, NPPC, ADRB2, ADBR1, MYH6, and PLN to be consequential based on our divergence analysis.
心血管疾病（CVD）是由多种复杂且在很大程度上可遗传的疾病引起的。鉴定关键基因并了解其在人类基因组中对 CVD 的易感性，有助于对相关患者进行早期诊断和个性化治疗。心力衰竭（HF）是 CVD 表型之一，其死亡率很高。在这项研究中，我们研究了主要与 HF 和其他 CVD 相关的基因。为了实现本研究的目标，我们构建了一个由 35 名同意参与的患者组成的队列，并对他们的基于血清的样本进行了测序。我们生成并处理了全基因组序列（WGS）数据，并进行了功能突变、剪接、变异分布和分化分析，以了解每种突变类型及其影响之间的关系。我们的变异和流行率分析发现 FLNA、CST3、LGALS3 和 HBA1 与许多富集途径有关。功能突变分析发现 ACE、MME、LGALS3、NR3C2、PIK3C2A、CALD1、TEK 和 TRPV1 是显著的、可能具有重要意义的基因。我们发现，内含子、5'侧翼、3'UTR 和 3'侧翼突变在 HF 和其他 CVD 基因中最为常见。错义突变在 HF 和其他 CVD 基因中不太常见，但具有更大的功能影响。根据我们的分化分析，我们报告 HBA1、FADD、NPPC、ADRB2、ADBR1、MYH6 和 PLN 是重要的。
