A male-specific association between AGTR1 hypermethylation and coronary heart disease

  • Xiaojing Li Key Laboratory of Ningbo First Hospital and Cardiovascular Center of Ningbo First Hospital, Ningbo University, Ningbo, China
  • Nan Wu Key Laboratory of Ningbo First Hospital and Cardiovascular Center of Ningbo First Hospital, Ningbo University, Ningbo, China
  • Huihui Ji Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, China
  • Yi Huang Key Laboratory of Ningbo First Hospital and Cardiovascular Center of Ningbo First Hospital, Ningbo University, Ningbo, China
  • Haochang Hu Key Laboratory of Ningbo First Hospital and Cardiovascular Center of Ningbo First Hospital, Ningbo University, Ningbo, China
  • Jiyi Li Key Laboratory of Ningbo First Hospital and Cardiovascular Center of Ningbo First Hospital, Ningbo University, Ningbo, China
  • Siyu Mi Key Laboratory of Ningbo First Hospital and Cardiovascular Center of Ningbo First Hospital, Ningbo University, Ningbo, China
  • Shiwei Duan Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, China https://orcid.org/0000-0001-7682-2877
  • Xiaomin Chen Key Laboratory of Ningbo First Hospital and Cardiovascular Center of Ningbo First Hospital, Ningbo University, Ningbo, China
Keywords: Coronary heart disease, CHD, AGTR1, DNA methylation, males, angiotensin II receptor type 1, HepG2 cells, 5-aza-2'-deoxycytidine

Abstract

The AGTR1 gene encodes angiotensin II receptor type 1, which is involved in cardiovascular diseases such as coronary heart disease (CHD). In the current study, we analyzed AGTR1 methylation level in a Han Chinese population by SYBR green-based quantitative methylation-specific PCR (qMSP). We collected blood samples from 761 CHD patients and 398 non-CHD controls at the Ningbo First Hospital. A data mining analysis was also performed to explore the association between AGTR1 methylation and AGTR1 gene expression, using datasets from the cBioPortal for Cancer Genomics and the Gene Expression Omnibus (GEO) database. Our results showed a significantly higher percentage of methylated reference (PMR) of AGTR1 in male CHD patients compared with male non-CHD controls (median PMR: 2.12% vs. 0.59%, p = 0.037). The data mining analysis showed that AGTR1 expression was significantly increased in human hepatoma HepG2 cells treated with the demethylation agent 5-aza-2'-deoxycytidine (fold = 3.12, p = 0.009). Further data mining analysis using the cholangiocarcinoma (TCGA, PanCancer Atlas) data indicated an inverse association between AGTR1 methylation and AGTR1 expression (r = -0.595, p = 1.29E-04). Overall, our results suggest that AGTR1 methylation is involved in the regulation of AGTR1 gene expression and that AGTR1 hypermethylation is associated with CHD in males. These findings may provide new clues about the pathogenesis of CHD.

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A male-specific association between AGTR1 hypermethylation and coronary heart disease
Published
2019-09-19
How to Cite
1.
Li X, Wu N, Ji H, Huang Y, Hu H, Li J, Mi S, Duan S, Chen X. A male-specific association between AGTR1 hypermethylation and coronary heart disease. Bosn J of Basic Med Sci [Internet]. 2019Sep.19 [cited 2019Nov.15];00. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/4321
Section
Biochemistry