title: Assessment of Human Tribbles Homolog 3 Genetic Variation (rs2295490) Effects on Type 2 Diabetes Patients with Glucose Control and Blood Pressure Lowering Treatment.
abstract: Effects of human tribbles homolog 3 (TRIB3) genetic variation (c.251 A>G, Gln84Arg, rs2295490) on the clinical outcomes of vascular events has not been evaluated in patients with type 2 diabetes after blood pressure lowering and glucose controlling treatment. We did an analysis of a 2×2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled clinical trial at 61 centers in China, with a follow-up period of 5years. The major vascular endpoints were the composites of death from cardio-cerebral vascular diseases, non-fatal stroke and myocardial infraction, new or worsening renal and diabetic eye disease. A total of 1884 participants were included in our research with a 4.8years median follow-up. For glucose lowering axis, patients with TRIB3 (rs2295490) AA (n=609) genotype exhibited significantly reduced risk of major vascular events compared with AG+GG (n=335) genotype carriers (Hazard ratio 0.72, 95% CI 0.55-0.94, p=0.016), Paradoxically, the risk of vascular events were significantly increased in patients with AA (n=621) compared to AG+GG (n=319) genotype for intensive glucose control (Hazard ratio 1.46, 95% CI, 1.06–2.17, p = 0.018) [corrected]. . For blood pressure lowering axis, marginally significant difference was found between TRIB3 variant and coronary events. Our findings suggest that good glucose and blood pressure control exhibited greater benefits on vascular outcomes in patients with TRIB3 (rs2295490) G allele.
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
authors: Fazhong
authors: F
authors: He
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
authors: Mouze
authors: M
authors: Liu
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
authors: Zhangren
authors: Z
authors: Chen
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
authors: Guojing
authors: G
authors: Liu
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
authors: Zhenmin
authors: Z
authors: Wang
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
authors: Rong
authors: R
authors: Liu
authors: Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
authors: Jianquan
authors: J
authors: Luo
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
authors: Jie
authors: J
authors: Tang
authors: Beijing Hypertension League Institute, 24 Shijingshan Road, Beijing 100043, China.
authors: Xingyu
authors: X
authors: Wang
authors: Beijing Hypertension League Institute, 24 Shijingshan Road, Beijing 100043, China.
authors: Xin
authors: X
authors: Liu
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
authors: Honghao
authors: H
authors: Zhou
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
authors: Xiaoping
authors: X
authors: Chen
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China.
authors: Zhaoqian
authors: Z
authors: Liu
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China. Electronic address: yjsd2003@163.com.
authors: Wei
authors: W
authors: Zhang
mesh_terms: D000368:Aged; D000483:Alleles; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000235:genetics*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D018797:Cell Cycle Proteins; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Hypertension; Individualized drug therapy; Pharmacogenetics; TRIB3; Type 2 diabetes