Division of Nephrology and Hypertension, University of Cape Town/Groote Schuur Hospital, Cape Town, South Africa.
PLoS One. 2010 Sep 27;5(9):e12989. doi: 10.1371/journal.pone.0012989.
Multiple factors underlie susceptibility to essential hypertension, including a significant genetic and ethnic component, and environmental effects. Blood pressure response of hypertensive individuals to salt is heterogeneous, but salt sensitivity appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select and prioritize candidate aetiological genes for salt-sensitive hypertension. Additionally, we have compared allele frequencies and copy number variation for single nucleotide polymorphisms in candidate genes between indigenous Southern African and Caucasian populations, with the aim of identifying candidate genes with significant variability between the population groups: identifying genetic variability between population groups can exploit ethnic differences in disease prevalence to aid with prioritisation of good candidate genes. Our top-ranking candidate genes include parathyroid hormone precursor (PTH) and type-1 angiotensin II receptor (AGTR1). We propose that the candidate genes identified in this study warrant further investigation as potential aetiological genes for salt-sensitive hypertension.
多种因素导致原发性高血压易感性，包括重要的遗传和种族因素以及环境影响。高血压个体对盐的血压反应存在异质性，但盐敏感性在非洲裔原住民中更为普遍。然而，盐敏感性高血压的潜在遗传机制尚不清楚。在这项研究中，我们使用了包括文本挖掘和数据挖掘在内的计算方法，选择和优先考虑盐敏感性高血压的候选病因基因。此外，我们比较了候选基因在南非土著和高加索人群中的单核苷酸多态性的等位基因频率和拷贝数变异，目的是确定人群之间具有显著变异性的候选基因：识别人群之间的遗传变异性可以利用疾病流行率的种族差异来帮助优先考虑候选基因。我们排名最高的候选基因包括甲状旁腺激素前体（PTH）和 1 型血管紧张素 II 受体（AGTR1）。我们提出，本研究中确定的候选基因值得进一步研究，作为盐敏感性高血压的潜在病因基因。
