Dataset Information

Serine hydroxymethyltransferase 1 promoter hypermethylation increases the risk of essential hypertension.

ABSTRACT:

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.

SUBMITTER: Xu G

PROVIDER: S-EPMC6818578 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Serine hydroxymethyltransferase 1 promoter hypermethylation increases the risk of essential hypertension.

Xu Guodong G Wang Changyi C Ying Xiuru X Kong Fanqian F Ji Huihui H Zhao Jinshun J Zhang Xiaohong X Duan Shiwei S Han Liyuan L Li Li L

Journal of clinical laboratory analysis 20181109 3

<h4>Background</h4>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).<h4>Methods</h4>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 SHM ...[more]

PMID: 30411815

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Project description:Serine hydroxymethyltransferase (SHMT), encoded by the glyA gene, is a ubiquitous pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the formation of glycine from serine. The thereby generated 5,10-methylene tetrahydrofolate (MTHF) is a major source of cellular one-carbon units and a key intermediate in thymidylate biosynthesis. While in virtually all eukaryotic and many bacterial systems thymidylate synthase ThyA, SHMT and dihydrofolate reductase (DHFR) are part of the thymidylate/folate cycle, the situation is different in organisms using flavin-dependent thymidylate synthase ThyX. Here the distinct catalytic reaction directly produces tetrahydrofolate (THF) and consequently in most ThyX-containing organisms, DHFR is absent. While the resulting influence on the folate metabolism of ThyX-containing bacteria is not fully understood, the presence of ThyX may provide growth benefits under conditions where the level of reduced folate derivatives is compromised. Interestingly, the third key enzyme implicated in generation of MTHF, serine hydroxymethyltransferase (SHMT), has a universal phylogenetic distribution, but remains understudied in ThyX-containg bacteria. To obtain functional insight into these ThyX-dependent thymidylate/folate cycles, we characterized the predicted SHMT from the ThyX-containing bacterium Helicobacter pylori. Serine hydroxymethyltransferase activity was confirmed by functional genetic complementation of a glyA-inactivated E. coli strain. A H. pylori ΔglyA strain was obtained, but exhibited markedly slowed growth and had lost the virulence factor CagA. Biochemical and spectroscopic evidence indicated formation of a characteristic enzyme-PLP-glycine-folate complex and revealed unexpectedly weak binding affinity of PLP. The three-dimensional structure of the H. pylori SHMT apoprotein was determined at 2.8Ǻ resolution, suggesting a structural basis for the low affinity of the enzyme for its cofactor. Stabilization of the proposed inactive configuration using small molecules has potential to provide a specific way for inhibiting HpSHMT.

Dataset Information

Serine hydroxymethyltransferase 1 promoter hypermethylation increases the risk of essential hypertension.

Background

Methods

Results

Conclusion

Publications

Serine hydroxymethyltransferase 1 promoter hypermethylation increases the risk of essential hypertension.

Similar Datasets

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