Author/Authors :
Xu, Guodong Medical Record Statistics Room - Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, PR China , Wang, Zhiyi Department of Preventive Medicine - Zhejiang Provincial Key Laboratory of Pathophysiology - School of Medicine - Ningbo University, Ningbo, Zhejiang, China , Li, Lian Department of Preventive Medicine - Zhejiang Provincial Key Laboratory of Pathophysiology - School of Medicine - Ningbo University, Ningbo, Zhejiang, China , Li, Wenxia Department of Preventive Medicine - Zhejiang Provincial Key Laboratory of Pathophysiology - School of Medicine - Ningbo University, Ningbo, Zhejiang, China , Hu, Jingcen Department of Preventive Medicine - Zhejiang Provincial Key Laboratory of Pathophysiology - School of Medicine - Ningbo University, Ningbo, Zhejiang, China , Wang, Shuyu Department of Preventive Medicine - Zhejiang Provincial Key Laboratory of Pathophysiology - School of Medicine - Ningbo University, Ningbo, Zhejiang, China , Deng, Hongxia Department of Otorhinolaryngology Head and Neck Surgery - Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China , Li, Bo Department of Non‑Communicable Disease Prevention and Control - Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, Guangdong, China , Wang, Changyi Department of Non‑Communicable Disease Prevention and Control - Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, Guangdong, China , Shen, Zhishen Department of Otorhinolaryngology Head and Neck Surgery - Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China , Han, Liyuan Hwa Mei Hospital - University of Chinese Academy of Sciences - Ningbo, Zhejiang, PR China
Abstract :
Background: DNA methylation was considered to play an important role in hypertension. However, the direct association between
dihydrofolate reductase (DHFR) promoter methylation and hypertension remains unclear. We thus aimed to investigate the
relationship between DNA methylation of DHFR promoter and hypertension. Materials and Methods: A total of 371 hypertensive
patients (diastolic blood pressure ≥90 mmHg and/or systolic blood pressure ≥140 mmHg or a history of antihypertensive treatment)
and 320 age‑ and sex‑matched healthy controls from the Hypertension Management Information System in Nanshan Community
Health Service Centers were included in this case–control study. Quantitative methylation‑specific polymerase chain reaction was
used to measure the level of DHFR promoter methylation, which was presented as the percentage of methylated reference (PMR).
A multivariate logistic regression model was used to explore the risk of DHFR promoter methylation. Results: Our results
indicated that the level of DHFR promoter methylation was higher in hypertensive patients (median PMR, 34.32%; interquartile
range, 11.34–119.60) than in healthy controls (median PMR, 18.45%; interquartile range, 8.16–35.40) (P < 0.001). Multivariable
analysis showed that the risk of DHFR promoter hypermethylation was significantly higher in hypertensive patients than in healthy
controls (odds ratio = 3.94, 95% confidence interval = 2.56–6.02, P < 0.001). Furthermore, hypermethylation was positively associated
with sex, high blood homocysteine levels, and alcohol drinking. In particular, the area under the receiver operating characteristic curve
was 0.688 (0.585–0.668) for the male hypertensive patients, suggesting the potential diagnostic value of DHFR promoter methylation
in male hypertension. Conclusion: Our results demonstrated that DHFR promoter hypermethylation is positively associated with
the risk of hypertension in Chinese.
