Correlation between miRNA target site polymorphisms in the 3' UTR of AVPR1A and the risk of hypertension in the Chinese Han population

Biosci Rep. 2019 May 14;39(5):BSR20182232. doi: 10.1042/BSR20182232. Print 2019 May 31.

Abstract

We aimed to study the relationship between rs11174811 and rs3803107 single nucleotide polymorphisms (SNPs) in miRNA target sites of the 3' UTR in the arginine vasopressin receptor 1a gene (AVPR1A) and the risk of hypertension in the Chinese Han population. The genotypes at rs11174811 and rs3803107 were analyzed by direct sequencing in 425 Chinese Han patients with hypertension and 425 healthy subjects. AVPR1A expression was investigated by transfecting miR-526b, miR-375, and miR-186 mimics into human umbilical vein endothelial cells (HUVECs) containing AVPR1A rs11174811 CC, CA/AA and AVPR1A rs3803107 GG, GA/AA genotypes. The A alleles of rs11174811 (adjusted OR = 1.424, 95% CI: 1.231-1.599, P<0.001) and rs3803107 (adjusted OR = 1.222, 95% CI: 1.092-1.355; P=0.001) were high risk factors for hypertension. Plasma levels of miR-526b, miR-375, and miR-186 were higher in the study group than in the control group (P<0.001). The expression levels of AVPR1A mRNA in AVPR1A rs11174811 and rs3803107 mutant HUVECs were higher than those in wild-type cells (t = 8.811, 4.068 and P=0.001, 0.015, respectively). The single nucleotide polymorphisms rs11174811 and rs3803107 in the AVPR1A gene are associated with an increased risk of hypertension in the Chinese Han population. This may be related to the effect of these variants on the regulation of AVPR1A expression by miRNAs.

Keywords: Arginine vasopressin receptor 1a; hypertension; microRNA; single nucleotide polymorphism.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People / genetics
  • China / epidemiology
  • Female
  • Genetic Predisposition to Disease
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hypertension / epidemiology
  • Hypertension / genetics*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, Vasopressin / genetics*

Substances

  • 3' Untranslated Regions
  • AVPR1A protein, human
  • MicroRNAs
  • Receptors, Vasopressin