Abstract
Essential hypertension is a common cardiovascular disease with complex etiology, closely related to genetic and environmental factors. The pathogenesis of hypertension involves alteration in vascular resistance caused by sympathetic nervous system (SNS) and renin angiotensin system (RAS). Susceptibility factors of hypertension vary with regions and ethnicities. In this study, we conducted target capture sequencing on 54 genes related to SNS and RAS derived from a collection of Han nationality, consisting of 151 hypertension patients and 65 normal subjects in Xinjiang, China. Six non-synonymous mutations related to hypertension were identified, including GRK4 rs1644731 and RDH8 rs1801058, Mutations are predicted to affect 3D conformation, force field, transmembrane domain and RNA secondary structure of corresponding genes. Based on protein interaction network and pathway enrichment, GRK4 is predicted to participate in hypertension by acting on dopaminergic synapse, together with interacting components. RDH8 is involved in vitamin A (retinol) metabolism and consequent biological processes related to hypertension. Thus, GRK4 and RDH8 may serve as susceptibility genes for hypertension. This finding provides new genetic evidence for elucidating risk factors of hypertension in Han nationality in Xinjiang, which in turn, enriches genetic resource bank of hypertension susceptibility genes.
Highlights
Essential hypertension (EH) is traditionally defined as persistently high blood pressure (HBP) with systolic blood pressure 140 mmHg and diastolic blood pressure 90 mmHg
The protein encoded by HPS3 may participate in organelle biogenesis associated with melanosomes, platelet dense granules and lysosomes
A family member of Fas activated serine/threonine kinase domain (FASTKD) encoded by FASTKD3 may be involved in apoptosis
Summary
Essential hypertension (EH) is traditionally defined as persistently high blood pressure (HBP) with systolic blood pressure 140 mmHg and diastolic blood pressure 90 mmHg. The prevalence of hypertension is expected to increase by 60% worldwide by 2025 [1]. High blood pressure is one of the leading causes of death in China. Identifies genetic variations in Han Chinese with essential hypertension in Xinjiang.
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