ASSOCIATIONS OF RENALASE WITH BLOOD PRESSURE AND THE RISK OF HYPERTENSION IN CHINESE ADULTS

Abstract

Objective: Renalase, a novel secretory flavoprotein with amine oxidase activity, is secreted into the blood by the kidneys and is hypothesized to participate in catecholamine metabolism. The aim of the study was to investigate the associations of renalase with blood pressure (BP) and the risk of hypertension from three perspectives of genetic variations, serum and kidney levels in humans. Design and method: 1. A total of 515 Chinese participants from 124 families were eligible for this study. We followed up this cohort in 2009, 2012 and 2018, respectively. 10 SNPs in renalase gene were genotyped to examine the associations with longitudinal BP changes and incident hypertension during 14 years of follow-up. 2. 2342 participants from the Hanzhong Adolescent Hypertension Study cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine the relationships between serum renalase and the risk of hypertension. 3. 204 patients undergoing renal biopsy were recruited from our hospital. Expression of renalase in renal biopsy specimens were measured by immunohistochemistry (IHC). Results: 1. During 14 years of follow-up, 160 (53.9%) participants developed hypertension. renalase SNPs rs10887800, rs796945, rs1935582, rs2296545 and rs2576178 were significantly associated with 14-year change in DBP while SNP rs7922058 was associated with longitudinal SBP change. In addition, SNPs rs796945, rs1935582 and rs2576178 were significantly associated with hypertension incidence over 14 years. Gene-based analysis found that renalase was significantly associated with hypertension incidence over 14-year follow-up. 2. Hypertensive subjects have higher levels of serum renalase than in the normotensive subjects. Serum renalase showed a linear association with increased BP (24.8, 25.6, 27.1, and 27.7 ug/mL for subjects with normotension, prehypertension, stage 1 and stage 2 hypertension). In addition, serum renalase [1.018 (1.006–1.030)] was significantly associated with the risk of hypertension in 2392 Chinese subjects. 3. The levels of SBP and DBP were positively correlated with the level of renalase in renal tubular epithelial cells (RTEC). The RTEC renalase expression was decreased in hypertensive patients compared to non-hypertensive patients. Conclusions: These findings indicate that renalase may play an important role in BP progression and development of hypertension.