Kao David P, Stevens Laura M, Hinterberg Michael A, Görg Carsten
University of Colorado School of Medicine, 12700 E 19th Ave Campus Box B-139, Aurora, CO, 80045, USA.
J Cardiovasc Transl Res. 2017 Jun;10(3):285-294. doi: 10.1007/s12265-017-9729-1. Epub 2017 Jan 19.
Little is known about genetics of heart failure with preserved ejection fraction (HFpEF) in part because of the many comorbidities in this population. To identify single-nucleotide polymorphisms (SNPs) associated with HFpEF, we analyzed phenotypic and genotypic data from the Cardiovascular Health Study, which profiled patients using a 50,000 SNP array. Results were explored using novel SNP- and gene-centric tools. We performed analyses to determine whether some SNPs were relevant only in certain phenotypes. Among 3804 patients, 7 clinical factors and 9 SNPs were significantly associated with HFpEF; the most notable of which was rs6996224, a SNP associated with transforming growth factor-beta receptor 3. Most SNPs were associated with HFpEF only in the absence of a clinical predictor. Significant SNPs represented genes involved in myocyte proliferation, transforming growth factor-beta/erbB signaling, and extracellular matrix formation. These findings suggest that genetic factors may be more important in some phenotypes than others.
关于射血分数保留的心力衰竭（HFpEF）的遗传学知之甚少，部分原因是该人群存在许多合并症。为了识别与HFpEF相关的单核苷酸多态性（SNP），我们分析了心血管健康研究中的表型和基因型数据，该研究使用50000个SNP芯片对患者进行了分析。使用新型的以SNP和基因为中心的工具探索结果。我们进行了分析，以确定某些SNP是否仅在某些表型中相关。在3804名患者中，7个临床因素和9个SNP与HFpEF显著相关；其中最值得注意的是rs6996224，一个与转化生长因子-β受体3相关的SNP。大多数SNP仅在没有临床预测指标的情况下与HFpEF相关。显著的SNP代表参与心肌细胞增殖、转化生长因子-β/表皮生长因子受体（erbB）信号传导和细胞外基质形成的基因。这些发现表明，遗传因素在某些表型中可能比其他表型更重要。
