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CBS promoter hypermethylation increases the risk of hypertension and stroke
Changyi Wang1,2,3,4, Guodong Xu5, Qi Wen4
1Integrated Chinese and Western Medicine Postdoctoral research station, Jinan University, Guangzhou, China.
Insights
Cystathionine β-synthase promoter hypermethylation is linked to increased hypertension and stroke risk. This finding is particularly significant in male patients, highlighting a potential biomarker for cardiovascular disease.
Area of Science:
- Biochemistry
- Genetics
- Cardiovascular Disease Research
Background:
- Cystathionine β-synthase (CBS) is crucial for homocysteine metabolism.
- Elevated homocysteine (hyperhomocysteinemia) is associated with hypertension and stroke.
- The role of CBS promoter methylation in these conditions requires investigation.
Purpose of the Study:
- To investigate the association between Cystathionine β-synthase promoter methylation and the risk of hypertension and stroke.
- To quantify CBS methylation levels in patients with hypertension and stroke compared to healthy controls.
Main Methods:
- Quantitative methylation-specific PCR was used to measure CBS promoter methylation levels.
- The study included 218 healthy individuals, 132 stroke patients, and 243 hypertensive patients.
- The 2-ΔΔCt method and percent methylated reference were used for analysis.
Main Results:
- CBS promoter methylation levels were significantly higher in hypertensive and stroke patients compared to healthy individuals.
- Hypermethylation of the CBS promoter was associated with an increased risk of hypertension (OR=1.035) and stroke (OR=1.015).
- The predictive value of CBS promoter methylation was notable in male patients with hypertension and stroke.
Conclusions:
- Cystathionine β-synthase promoter hypermethylation is a risk factor for developing hypertension and stroke.
- The findings suggest a potential role for CBS methylation as a biomarker, especially in males.
- Further research may elucidate the precise mechanisms linking CBS methylation to cardiovascular events.
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 2-ΔΔCt 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.
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