Hypertension is a disease of multifactorial origin, involving environmental factors as well as genetic factors arising from a number of susceptibility genes. These genes may contribute to between 30 and 50% of the variations in blood pressure seen among individuals.1 Despite recent significant advances in genomic and statistical tools, a genetics-based approach to human hypertension remains a major challenge. Recently, numerous roles have been defined for the endothelium, including the regulation of vascular tone, modulation of inflammation, regulation of vascular growth and modulation of platelet aggregation and coagulation, in addition to its traditional role as the barrier to prevent influx of plasma components and blood cells from the vascular lumen. Disruption of these properties is termed endothelial dysfunction and can be demonstrated as an impaired vasorelaxation response to endothelium-dependent vasodilators.2

E-selectin is a cell-surface glycoprotein expressed on endothelial cells after activation by cytokines, and it mediates the adhesion of circulating monocytes and lymphocytes to endothelial cells. This adherence to the activated arterial endothelium is one of the earliest detectable events in the pathogenesis of atherosclerosis.3 The inflammatory process induces the expression of adhesion molecules, which interact with leukocyte integrins and promote the atherothrombotic process at the surface of endothelial cells.4, 5 E-selectin is expressed only by activated endothelium; however, its circulating form can be found in the plasma after enzymatic cleavage or shedding by damaged or activated endothelial cells. Acute or chronic inflammation may damage the endothelium, and cytokines such as interleukin-1 or tumor necrosis factor-α also increase the level of soluble E-selectin via immunological activation, as shown by in vitro studies.6 Under high blood pressure conditions, sheer stress may induce a situation in which endothelial cells are activated and/or damaged. Hypertensive patients exhibit elevated soluble E-selectin levels compared with controls, and there is a positive correlation between soluble E-selectin and diastolic blood pressure in these patients.7, 8

From these observations, the E-selectin gene seems to be an attractive candidate gene for endothelial dysfunction related to hypertension.

Wang et al.9 investigated the association between genetic variants in the E-selectin gene and essential hypertension in Han, Kazakh and Uygur populations in China. They found an association of E-selectin gene variants with essential hypertension in these populations. A common variant of the E-selectin gene was strongly associated with essential hypertension in the Han population. This report suggests that E-selectin has an important role in the development of hypertension through causing the impairment of endothelial function. As China is a very large multiethnic country with 56 identified ethnic groups, and some of the minor ethnic groups are genetically isolated from other groups, performing genetic association analysis in different ethnic groups in China is likely to be informative in searching for candidate genes for diseases associated with each ethnic group.

The genetics of hypertension are complex. No known single gene has a major role; instead, many genes, each with mild effects, interact with different environmental stimuli and contribute to the blood pressure. This study unraveled the importance of the E-selectin gene as one of the genetic factors affecting blood pressure regulation. The accumulated results from studies exploring hypertension-related genes with mild effects must, on the whole, shape the understanding of this complex trait disease in the future. Moreover, further studies of gene–gene or gene–environment interaction will be necessary.