Association of AGTR1 Promoter Methylation Levels with Essential Hypertension Risk: A Matched Case-Control Study

Cytogenet Genome Res. 2015;147(2-3):95-102. doi: 10.1159/000442366. Epub 2015 Dec 12.

Abstract

The purpose of the present study was to investigate whether methylation of the angiotensin II type 1 receptor (AGTR1) promoter contributed to the risk of essential hypertension (EH). A total of 96 EH cases and 96 gender- and age-matched healthy controls were recruited. Methylation of 8 CpG dinucleotides (CpG1-8) in the AGTR1 promoter was examined using the bisulphite pyrosequencing technology. Three CpG dinucleotides (CpG6-8) could not be well sequenced, therefore only the remaining 5 CpG sites were analysed. A significantly lower CpG1 methylation level was identified in EH cases than in controls (cases vs.

Controls: 6.74 ± 4.32% vs. 9.66 ± 5.45%, p = 0.007), and no significant association was observed in the remaining analyses. In addition, significantly lower CpG1 (p = 0.028) and higher CpG2 (p = 0.032) methylation levels were observed in males than in females. In the breakdown association test by gender, a higher CpG1 methylation level was also identified in EH in both males (p = 0.034) and females (p = 0.020). Receiver operating characteristic curves showed that CpG1 methylation was a significant predictor of EH. Furthermore, CpG1 methylation was inversely correlated with uric acid levels in controls. The present study suggests that CpG1 hypomethylation in the AGTR1 promoter is likely associated with the risk of EH in the population assessed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Pressure
  • Body Mass Index
  • Case-Control Studies
  • Cholesterol / blood
  • CpG Islands / genetics
  • DNA Methylation*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Hypertension / blood
  • Hypertension / genetics*
  • Hypertension / physiopathology
  • Lipoproteins, HDL / blood
  • Lipoproteins, LDL / blood
  • Logistic Models
  • Male
  • Middle Aged
  • Promoter Regions, Genetic / genetics*
  • Receptor, Angiotensin, Type 1 / genetics*
  • Risk Factors
  • Sequence Analysis, DNA / methods
  • Triglycerides / blood

Substances

  • AGTR1 protein, human
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Receptor, Angiotensin, Type 1
  • Triglycerides
  • Cholesterol