Assessment of Human Tribbles Homolog 3 Genetic Variation (rs2295490) Effects on Type 2 Diabetes Patients with Glucose Control and Blood Pressure Lowering Treatment

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.