Polytropic Influence of TRIB3 rs2295490 Genetic Polymorphism on Response to Antihypertensive Agents in Patients With Essential Hypertension

Jiecan Zhou; Jiecan Zhou; Jiecan Zhou; Jiecan Zhou; Fazhong He; Fazhong He; Fazhong He; Bao Sun; Bao Sun; Bao Sun; Rong Liu; Rong Liu; Rong Liu; Yongchao Gao; Yongchao Gao; Yongchao Gao; Huan Ren; Huan Ren; Huan Ren; Yan Shu; Xiaoping Chen; Xiaoping Chen; Xiaoping Chen; Zhaoqian Liu; Zhaoqian Liu; Zhaoqian Liu; Honghao Zhou; Honghao Zhou; Honghao Zhou; Sheng Deng; Heng Xu; Jianmin Li; Linyong Xu; Wei Zhang; Wei Zhang; Wei Zhang

doi:10.3389/fphar.2019.00236

Frontiers in Pharmacology (Mar 2019)

Polytropic Influence of TRIB3 rs2295490 Genetic Polymorphism on Response to Antihypertensive Agents in Patients With Essential Hypertension

Jiecan Zhou,
Jiecan Zhou,
Jiecan Zhou,
Jiecan Zhou,
Fazhong He,
Fazhong He,
Fazhong He,
Bao Sun,
Bao Sun,
Bao Sun,
Rong Liu,
Rong Liu,
Rong Liu,
Yongchao Gao,
Yongchao Gao,
Yongchao Gao,
Huan Ren,
Huan Ren,
Huan Ren,
Yan Shu,
Xiaoping Chen,
Xiaoping Chen,
Xiaoping Chen,
Zhaoqian Liu,
Zhaoqian Liu,
Zhaoqian Liu,
Honghao Zhou,
Honghao Zhou,
Honghao Zhou,
Sheng Deng,
Heng Xu,
Jianmin Li,
Linyong Xu,
Wei Zhang,
Wei Zhang,
Wei Zhang

Affiliations

Jiecan Zhou: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
Jiecan Zhou: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China
Jiecan Zhou: National Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, China
Jiecan Zhou: Pharmacy Department, The First Affiliated Hospital, University of South China, Hengyang, China
Fazhong He: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
Fazhong He: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China
Fazhong He: National Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, China
Bao Sun: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
Bao Sun: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China
Bao Sun: National Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, China
Rong Liu: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
Rong Liu: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China
Rong Liu: National Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, China
Yongchao Gao: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
Yongchao Gao: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China
Yongchao Gao: National Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, China
Huan Ren: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
Huan Ren: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China
Huan Ren: National Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, China
Yan Shu: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, United States
Xiaoping Chen: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
Xiaoping Chen: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China
Xiaoping Chen: National Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, China
Zhaoqian Liu: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
Zhaoqian Liu: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China
Zhaoqian Liu: National Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, China
Honghao Zhou: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
Honghao Zhou: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China
Honghao Zhou: National Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, China
Sheng Deng: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China
Heng Xu: Department of Laboratory Medicine, Precision Medicine Center, and Precision Medicine Key Laboratory of Sichuan Province, Collaborative Innovation Center, West China Hospital, Sichuan University, Chengdu, China
Jianmin Li: Department of Respiratory Medicine, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China
Linyong Xu: Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
Wei Zhang: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China
Wei Zhang: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, China
Wei Zhang: National Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, China

DOI: https://doi.org/10.3389/fphar.2019.00236
Journal volume & issue: Vol. 10

Abstract

Read online

Tribbles homolog 3 (TRIB3) mediating signaling pathways are closely related to blood pressure regulation. Our previous findings suggested a greater benefit on vascular outcomes in patients carrying TRIB3 (251, A > G, rs2295490) G allele with good glucose and blood pressure control. And TRIB3 (rs2295490) AG/GG genotypes were found to reduce primary vascular events in type 2 diabetic patients who received intensive glucose treatment as compared to those receiving standard glucose treatment. However, the effect of TRIB3 genetic variation on antihypertensives was not clear in essential hypertension patients. A total of 368 patients treated with conventional dosage of antihypertensives (6 groups, grouped by atenolol/bisoprolol, celiprolol, doxazosin, azelnidipine/nitrendipine, imidapril, and candesartan/irbesartan) were enrolled in our study. Genetic variations were successfully identified by sanger sequencing. A linear mixed model analysis was performed to evaluate blood pressures among TRIB3 (251, A > G) genotypes and adjusted for baseline age, gender, body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol and other biochemical factors appropriately. Our data suggested that TRIB3 (251, A > G) AA genotype carriers showed better antihypertensive effect than the AG/GG genotype carriers [P = 0.014 for DBP and P = 0.042 for mean arterial pressure (MAP)], with a maximal reduction of DBP by 4.2 mmHg and MAP by 3.56 mmHg after azelnidipine or nitrendipine treatment at the 4th week. Similar tendency of DBP-change and MAP-change was found for imidapril (ACEI) treatment, in which marginally significances were achieved (P = 0.073 and 0.075, respectively). Against that, we found that TRIB3 (251, A > G) AG/GG genotype carriers benefited from antihypertensive therapy of ARBs with a larger DBP-change during the period of observation (P = 0.036). Additionally, stratified analysis revealed an obvious difference of the maximal blood pressure change (13 mmHg for the MAP between male and female patients with AA genotype who took ARBs). Although no significant difference in antihypertensive effect between TRIB3 (251, A > G) genotypes in patients treated with α, β-ADRs was observed, we found significant difference in age-, sex-dependent manner related to α, β-ADRs. In conclusion, our data supported that TRIB3 (251, A > G) genetic polymorphism may serve as a useful biomarker in the treatment of hypertension.

Published in Frontiers in Pharmacology

ISSN: 1663-9812 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://journal.frontiersin.org/journals/pharmacology

About the journal

Abstract

Keywords