Polytropic Influence of TRIB3 rs2295490 Genetic Polymorphism on Response to Antihypertensive Agents in Patients With Essential Hypertension
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...
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00236/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jiecan Zhou |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T02:11:31Z |
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| language | English |
| last_indexed | 2024-12-20T02:11:31Z |
| publishDate | 2019-03-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-eff766fc509448cfa958598304ca0d172022-12-21T19:57:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-03-011010.3389/fphar.2019.00236440718Polytropic Influence of TRIB3 rs2295490 Genetic Polymorphism on Response to Antihypertensive Agents in Patients With Essential HypertensionJiecan Zhou0Jiecan Zhou1Jiecan Zhou2Jiecan Zhou3Fazhong He4Fazhong He5Fazhong He6Bao Sun7Bao Sun8Bao Sun9Rong Liu10Rong Liu11Rong Liu12Yongchao Gao13Yongchao Gao14Yongchao Gao15Huan Ren16Huan Ren17Huan Ren18Yan Shu19Xiaoping Chen20Xiaoping Chen21Xiaoping Chen22Zhaoqian Liu23Zhaoqian Liu24Zhaoqian Liu25Honghao Zhou26Honghao Zhou27Honghao Zhou28Sheng Deng29Heng Xu30Jianmin Li31Linyong Xu32Wei Zhang33Wei Zhang34Wei Zhang35Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaPharmacy Department, The First Affiliated Hospital, University of South China, Hengyang, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, United StatesDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Laboratory Medicine, Precision Medicine Center, and Precision Medicine Key Laboratory of Sichuan Province, Collaborative Innovation Center, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Respiratory Medicine, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, ChinaDepartment of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, ChinaPharmacogenetics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatrics, Xiangya Hospital, Central South University, Changsha, ChinaTribbles 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.https://www.frontiersin.org/article/10.3389/fphar.2019.00236/fullTRIB3rs2295490polymorphismantihypertensive agentsessential hypertension |
| spellingShingle | 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 Polytropic Influence of TRIB3 rs2295490 Genetic Polymorphism on Response to Antihypertensive Agents in Patients With Essential Hypertension Frontiers in Pharmacology TRIB3 rs2295490 polymorphism antihypertensive agents essential hypertension |
| title | Polytropic Influence of TRIB3 rs2295490 Genetic Polymorphism on Response to Antihypertensive Agents in Patients With Essential Hypertension |
| title_full | Polytropic Influence of TRIB3 rs2295490 Genetic Polymorphism on Response to Antihypertensive Agents in Patients With Essential Hypertension |
| title_fullStr | Polytropic Influence of TRIB3 rs2295490 Genetic Polymorphism on Response to Antihypertensive Agents in Patients With Essential Hypertension |
| title_full_unstemmed | Polytropic Influence of TRIB3 rs2295490 Genetic Polymorphism on Response to Antihypertensive Agents in Patients With Essential Hypertension |
| title_short | Polytropic Influence of TRIB3 rs2295490 Genetic Polymorphism on Response to Antihypertensive Agents in Patients With Essential Hypertension |
| title_sort | polytropic influence of trib3 rs2295490 genetic polymorphism on response to antihypertensive agents in patients with essential hypertension |
| topic | TRIB3 rs2295490 polymorphism antihypertensive agents essential hypertension |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00236/full |
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