Association study between biomarkers of metabolites and its relevance genes for hypertension in Korean adults

Abstract

Abstract Metabolites are the intermediate and end-products of metabolic pathways that reflect ongoing biological processes. Unlike genes and proteins, metabolites are closely related to biochemical activities and clinical phenotypes, which can serve as indicators and characterize their impact on disease. Hypertension (HTN) is among the most important preclinical conditions of metabolic syndrome and remains the top risk factor for cardiovascular diseases. Pathophysiological mechanisms for the development of HTN are well known. However, there is a lack of knowledge regarding the metabolite changes that promote disease development. Therefore, we investigated HTN-related metabolites using the cohort data of the Korean Genome and Epidemiology Study (KoGES). As a result, phosphatidylcholine (PC)-derived metabolites were found to have the highest correlation with HTN. In linear regression analysis between metabolites and single nucleotide polymorphisms (SNPs), the SNPs belonging to the HECT domain E3 ubiquitin protein ligase 4 (HECTD4), myelin regulatory factor (MYRF), and fatty acid desaturase 1 (FADS1) genes showed a significant correlation. Among them, rs11066280 of the HECTD4 gene was found to be related to HTN (p = 0.03). This result was consistent with the reported association of HECTD4 with systolic and diastolic blood pressure. In conclusion, PC-derived metabolites and HECTD4 are associated with HTN in the Korean population. With the identification of HTN-related metabolites, the results of this study could be very useful in the early detection, diagnosis, and treatment of HTN. Finally, if in vitro and in vivo data are added in the future could help in the formulation of new guidelines for the treatment of HTN.