Common variants in TGFBR2 and miR-518 genes are associated with hypertension in the Chinese population

Am J Hypertens. 2014 Oct;27(10):1268-76. doi: 10.1093/ajh/hpu047. Epub 2014 Mar 31.

Abstract

Background: An animal study reported that TGF-β1 maturation was linked to the homeostasis of blood pressure and elastogenesis of essential hypertension (EH). Recent advances require further research of TGF-β1 receptor in EH.

Methods: A case-control study comprised of 2,012 adult hypertension case patients and 2,210 adult control subjects was conducted, and the association with blood pressure was further tested in children. Logistic regression and calculated genetic risk score were used to evaluate the effects of one single nucleotide polymorphism (SNP) and multiple SNPs on EH, respectively.

Results: The genetic risk score of 10 SNPs showed a significant association with hypertension; the odds ratio of the upper quartile vs. the lower quartile was 1.282 (P = 4.67 × 10(-3)). rs7256241 in miR-518 was significantly associated with diastolic blood pressure (DBP) change in control subjects (P = 0.002), and this association was also observed in children (P = 0.04). The systolic blood pressure (SBP) and DBP of female patients taking reserpine were higher with the C and G alleles of rs3773661 (P = 0.004) and rs7256241 (P = 0.002), respectively. In patients taking Zhen Ju Jiang Ya tablets, SBP and DBP decreased linearly with rs749794 (P = 0.004 and P = 0.048, respectively). SBP decreased linearly with rs1155705 (P = 0.007) and rs11709624 (P = 0.04), but increased with rs1036096 (P = 0.03) in male patients. In male patients taking Jiang Ya tablets, SBP increased linearly with rs11709624 (P = 0.007), DBP increased linearly with rs1155705 (P = 0.03) whereas decreased with rs7256241 (P = 0.04).

Conclusions: Our results suggest that TGFBR2 and miR-518 harbor variants that increase the risk of EH and affect blood pressure homeostasis as well as efficacy of antihypertensive agents.

Keywords: TGF-β1 receptor 2 gene.; association studies; blood pressure; hypertension; miR-518 gene; transforming growth factor β1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antihypertensive Agents / therapeutic use
  • Asian People / genetics*
  • Case-Control Studies
  • Child
  • Chrysanthemum
  • Clonidine / therapeutic use
  • Dihydralazine / therapeutic use
  • Drug Combinations
  • Drugs, Chinese Herbal / therapeutic use*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Hydrochlorothiazide / therapeutic use
  • Hypertension / drug therapy
  • Hypertension / genetics*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Promethazine / therapeutic use
  • Protein Serine-Threonine Kinases / genetics*
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics*
  • Reserpine / therapeutic use
  • Rutin / therapeutic use

Substances

  • Antihypertensive Agents
  • Drug Combinations
  • Drugs, Chinese Herbal
  • MIRN518 microRNA, human
  • MicroRNAs
  • Receptors, Transforming Growth Factor beta
  • Hydrochlorothiazide
  • Rutin
  • Reserpine
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Promethazine
  • Clonidine
  • Dihydralazine