Hypermethylation of dihydrofolate reductase promoter increases the risk of hypertension in Chinese

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.

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.

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.

Our results demonstrated that DHFR promoter hypermethylation is positively associated with the risk of hypertension in Chinese.