Assessment of Human Tribbles Homolog 3 Genetic Variation (rs2295490) Effects on Type 2 Diabetes Patients with Glucose Control and Blood Pressure Lowering Treatment.
Assessment of Human Tribbles Homolog 3 Genetic Variation (rs2295490) Effects on Type 2 Diabetes Patients with Glucose Control and Blood Pressure Lowering Treatment.
复制标题
评估人类 Tribbles 同源物 3 遗传变异 (rs2295490) 对 2 型糖尿病患者血糖控制和降压治疗的影响
DOI：
10.1016/j.ebiom.2016.10.025
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发表时间：
2016-11
期刊：
影响因子：
11.1
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
He F;Liu M;Chen Z;Liu G;Wang Z;Liu R;Luo J;Tang J;Wang X;Liu X;Zhou H;Chen X;Liu Z;Zhang W
在2型糖尿病患者中，尚未评估人类Tribbles同源物3（TRIB 3）遗传变异（c.251 A> G，Gln84Arg，rs2295490）对血管事件临床结局的影响。我们对中国61个中心的2 × 2析因（血糖控制轴和降压轴）随机对照临床试验进行了分析，随访期为5年。主要血管终点是心脑血管疾病死亡、非致死性卒中和心肌梗死、新发或恶化的肾脏疾病和糖尿病性眼病的复合终点。共有1884名参与者被纳入我们的研究，中位随访时间为4.8年。对于降糖轴，TRIB 3患者（rs2295490）AA（n = 609）基因型与AG + GG（n = 335）基因型携带者相比，主要血管事件的风险显著降低（风险比0.72，95% CI 0.55 - 0.94，p = 0.016），特别是，与AG + GG（n = 319）基因型相比，AA（n = 621）基因型患者强化血糖控制的血管事件风险显著增加（风险比1.46，95% CI，1.06 - 2.17，35 p = 0.018）。对于血压降低轴，TRIB3变异体和冠状动脉事件之间存在轻微显著差异。我们的研究结果表明，良好的血糖和血压控制对TRIB 3（rs2295490）G等位基因患者的血管结局具有更大的益处。TRIB3 rs2295490基因变异是与2型糖尿病血管并发症相关的血糖状态特异性。良好的血糖控制对TRIB 3 rs2295490 G等位基因患者的血管结局具有更大的益处。本研究提示TRIB 3 rs2295490基因变异可能是个体化药物治疗的一个有用的生物标志物。人tribbles同源物3（TRIB 3）已被报道为可抑制Akt磷酸化活化的假激酶。TRIB 3的过度活性可介导胰岛素抵抗和葡萄糖毒性。此外，TRIB 3在调节内皮细胞功能方面也具有不可或缺的作用。我们的研究显示TRIB3基因变异（rs2295490）是与2型糖尿病患者血管并发症相关的血糖状态特异性。此外，良好的血糖和血压控制对TRIB 3（rs2295490）G等位基因患者的血管结局表现出更大的益处。我们的发现表明，这种遗传变异可能是有用的生物标志物，为个别药物治疗。
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 5 years. 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 4.8 years 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, 35 p = 0.018). 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. TRIB3 rs2295490 genetic variation is glycemic-status-specific associated with vascular complications in type 2 diabetes. Good glucose control exhibited greater benefits on vascular outcomes in patients with TRIB3 rs2295490 G allele. Our study suggested TRIB3 rs2295490 genetic variation might be a useful biomarker for individualized drug therapy. Human tribbles homolog 3 (TRIB3) has been reported as a pseudo-kinase that can inhibit Akt phosphorylation activation. Over-activity of TRIB3 can mediate insulin resistance and glucose toxicity. In addition, TRIB3 also has an integral role in regulating the endothelial cells function. Our study revealed TRIB3 genetic variation (rs2295490) is glycemic-status-specific associated with vascular complications in patients with type 2 diabetes. Moreover, good glucose and blood pressure control exhibited greater benefits on vascular outcomes in patients with TRIB3 (rs2295490) G allele. Our finding suggests that this genetic variation might be useful as a biomarker for individual drug therapy.