miR-3188 (rs7247237-C>T) Single-Nucleotide Polymorphism Is Associated With the Incidence of Vascular Complications in Chinese Patients With Type 2 Diabetes

J Cardiovasc Pharmacol. 2019 Jul;74(1):62-70. doi: 10.1097/FJC.0000000000000681.

Abstract

miR-3188, one of the earliest discovered microRNAs, is involved in regulating the mTOR-p-PI3K/AKT pathway, thus affecting the progression of diabetic complications. In this study, we observed that the miR-3188 (rs7247237-C>T) polymorphism not only affected the production of nitric oxide (NO) production in endothelial cells, but also significantly associated with the incidence of vascular complications in Chinese patients with type 2 diabetes. Mechanistic analyses indicate that miR-3188 (rs7247237-T) polymorphism inhibited its own expression and upregulated the expression of gstm1 and trib3, which impairs NO production in human endothelial cells through inactivating AKT/eNOS signal transduction pathway. In addition, our clinical retrospective study indicated that, compared with patients with the CC genotype (n = 351), patients with rs7247237 TT + CT genotypes (n = 580) exhibited an increased risk of major vascular events during intensive glucose control treatment (hazard ratio = 1.560; 95% CI: 1.055-2.307, P = 0.025). Simultaneously, the risk of major vascular events was marginally decreased in patients with the CC genotype during intensive glucose control treatment compared with standard treatment (hazard ratio = 0.666; 95% CI: 0.433-1.016, P = 0.053). Our findings indicate that the miR-3188 (rs7247237-C>T) polymorphism is associated with the incidence of vascular complications in Chinese patients with type 2 diabetes, likely due to its remarkable effect on miR-3188 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asian People / genetics
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cells, Cultured
  • China / epidemiology
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Angiopathies / ethnology
  • Diabetic Angiopathies / genetics*
  • Diabetic Angiopathies / metabolism
  • Diabetic Angiopathies / prevention & control
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Incidence
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Multicenter Studies as Topic
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Phosphorylation
  • Polymorphism, Single Nucleotide*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • MIRN3188 microRNA, human
  • MicroRNAs
  • Nitric Oxide
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Proto-Oncogene Proteins c-akt