Open AccessSerine hydroxymethyltransferase 1 promoter hypermethylation increases the risk of essential hypertension
Author(s) -
Xu Guodong,
Wang Changyi,
Ying Xiuru,
Kong Fanqian,
Ji Huihui,
Zhao Jinshun,
Zhang Xiaohong,
Duan Shiwei,
Han Liyuan,
Li Li
Publication year - 2019
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.22712
Subject(s) - methylation , dna methylation , promoter , methylenetetrahydrofolate reductase , luciferase , serine hydroxymethyltransferase , biology , odds ratio , medicine , microbiology and biotechnology , gene expression , gene , endocrinology , chemistry , serine , genotype , transfection , genetics , biochemistry , enzyme
Background Serine hydroxymethyltransferase 1 (SHMT1) is an enzyme involved in folic acid metabolism and is known to contribute to the development of hypertension. We evaluated the relationship between SHMT1 promoter methylation and essential hypertension (EH). Methods Quantitative methylation‐specific polymerase chain reaction was used to measure the SHMT1 promoter methylation level in 241 EH patients and 288 age‐ and gender‐matched healthy individuals. The diagnostic value of SHMT1 promoter hypermethylation was analyzed using a receiver operating characteristic (ROC) curve. The Gene Expression Omnibus (GEO) database and dual‐luciferase reporter assay were used to validate our findings. Results Compared with the control group, significant differences in SHMT1 promoter methylation were found in both EH and hyperhomocysteinemia groups ( P < 0.001 and P = 0.029, respectively). The area under the curve of the diagnosis of SHMT1 promoter hypermethylation for EH was 0.808, with a sensitivity and specificity of 73.9% and 77.8%, respectively. The risk of SHMT1 promoter hypermethylation was significantly higher in the >65‐year group than in the ≤65‐year group (odds ratio = 3.925; 95% confidence interval = 2.141‐7.196). In addition, GEO database analysis showed that 5‐aza‐deoxycytidine increased gene expression in several carotid endothelial cell lines. A dual‐luciferase reporter assay revealed that the target sequence in the SHMT1 promoter upregulated gene expression. Conclusion Our findings indicate that SHMT1 promoter hypermethylation increases the risk of EH and may be a promising biomarker for EH.