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CBS promoter hypermethylation increases the risk of hypertension and stroke

OBJECTIVES:

Cystathionine β-synthase is a major enzyme in the metabolism of plasma homocysteine. Hyperhomocysteinemia is positively associated with hypertension and stroke. The present study was performed to examine the possible effects of Cystathionine β-synthase promoter methylation on the development of hypertension and stroke.

METHODS:

Using quantitative methylation-specific PCR, we determined the Cystathionine β-synthase methylation levels in 218 healthy individuals and 132 and 243 age- and gender-matched stroke and hypertensive patients, respectively. The relative changes in Cystathionine β-synthase promoter methylation were analyzed using the 2ΔΔCt method. The percent of the methylated reference of Cystathionine β-synthase was used to represent the Cystathionine β-synthase promoter methylation levels.

RESULTS:

In this study, the Cystathionine β-synthase promoter methylation levels of hypertensive and stroke participants were both higher than that of the healthy individuals (median percentages of the methylated reference were 50.61%, 38.05% and 30.53%, respectively, all p<0.001). Multivariable analysis showed that Cystathionine β-synthase promoter hypermethylation increased the risk of hypertension [odds ratio, OR (95% confidence interval, CI)=1.035 (1.025–1.045)] and stroke [OR (95% CI)=1.015 (1.003–1.028)]. The area under the curve of Cystathionine β-synthase promoter methylation was 0.844 (95% CI: 0.796–0.892) in male patients with hypertension and 0.722 (95% CI: 0.653–0.799) in male patients with stroke.

CONCLUSION:

Cystathionine β-synthase promoter hypermethylation increases the risk of hypertension and stroke, especially in male patients.

KEYWORDS:
CBS; Hypermethylation; Hypertension; Stroke; Homocysteine


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