Table 5.

Evidence of genes containing sentinel variants for roles in hypertension.

Gene	Evidence of role in hypertension
COL6A1	Encodes a collagen VI protein and provides structural support for a variety of tissues including the heart; has been shown previously, in addition to other VEGF-A pathway genes, to be associated with atrioventricular septal defect (AVSD) in patients with Down syndrome [63]
SLC28A3	Encodes a sodium-dependent nucleoside transporter (NT); NTs have many physiological regulatory roles including that of mediating adenosine concentration, which in turn affects vascular tone [64, 65]
SEL1L3	Differentially expressed between male familial combined hyperlipidemia and coronary heart disease (FCHL-CHD) patients and non-FCHL-non-CHD controls in a microarray study [66]. Also upregulated with a >6-fold expression change in a rabbit microarray study comparing simulating conditions before and after repair of coarctation of the aorta, a condition which may evolve into chronic hypertension [67]; as the authors stated, despite the surgically induced return to normal BP, the vasculature still retains its physical defects, and this gene may thus play a role in the continued residual effects.
YOD1	A deubiquitinase, targeted by miR-21 in the distal small pulmonary arteries of mice with pulmonary arterial hypertension exposed to hypoxic conditions, as well as in human pulmonary artery smooth muscle cells with transfected miR-21 [68].
CCDC13	Encodes a centriolar satellite protein involved in primary ciliogenesis [44]; this supports a potential role in hypertension present in individuals with autosomal dominant polycystic kidney disease, in which impaired primary cilia affects vascular tone [70, 71]
QSOX1	Recent experiments support cardiovascular function for QSOX1, encoding a sulfhydryl oxidase enzyme; one such function includes its induction of vascular smooth muscle cell migration and proliferation in vitro [72], a potential role in atherosclerosis [73], and its feasibility as a biomarker for acute decompensated heart failure [74, 75].