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 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.

Intensive Glucose Control Reduces the Risk Effect of TRIB3, SMARCD3, and ATF6 Genetic Variation on Diabetic Vascular Complications

“…We performed a retrospective pharmacogenomic analysis using samples and data from a 2 × 2 factorial randomized controlled trial conducted in 61 centers in China over a follow-up period of 5 years. The original study protocol and details have been published previously (Patel et al, 2007; Group et al, 2008; He et al, 2016). Briefly, approval to conduct the trial was obtained from the ethics committee of each study center, and informed consent was obtained from all subjects (registration number NCT00145925).…”

“…Specifically, patients with AG or GG genotypes experienced significantly fewer primary vascular events after receiving intensive glucose control treatment [aiming for a hemoglobin (Hb) A1c value of 6.5% or lower] as compared with patients receiving standard glucose treatment (patients who continued with their usual glucose control regimens). However, such a benefit was not observed in patients with the AA genotype (He et al, 2016). T2DM is a disease with complex traits, and a previous study suggested that core disease-related genes and genes outside of core pathways are sufficiently interconnected to affect its heritability (Boyle et al, 2017).…”

High glucose contributes to the proliferation and migration of non-small-cell lung cancer cells via GAS5-TRIB3 axis

“…A recent study identified that TRIB3 was up-regulated in NSCLC that promoted the metastasis and tumor growth [ 17 ]. Furthermore, TRIB3 has a pivotal role in insulin signaling transduction pathway [ 18 ], and the DM-induced tumor progression [ 19 ]. Thus, it is reasonable to infer that TRIB3 may participate in the development of NSCLC induced by HG.…”

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

“…These data indicate that TRIB3 has an integral role in regulating the blood pressure, and its genetic variation (251, A > G) may cause a variability of antihypertensive drug therapy. Our previous findings have suggested a greater benefit on vascular outcomes in patients carrying TRIB3 (rs2295490) G allele with good glucose and blood pressure control (He et al, 2016). TRIB3 (rs2295490) AG/GG genotypes were found to reduce primary vascular events in patients who received intensive glucose treatment as compared to those receiving standard glucose treatment in type 2 diabetic patients (He et al, 2018).…”