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High MTHFR promoter methylation levels in men confer protection against ischemic stroke

The MTHFR gene encodes methylenetetrahydrofolate reductase required for the metabolism of homocysteine (Hcy) – a previously reported independent risk factor for ischemic stroke (IS). In this study, we first aimed to clarify the association between DNA methylation levels in the MTHFR promoter and the...

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Autores principales: Xu, Shan, Shi, Qianping, Li, Bo, Han, Liyuan, Xu, Guodong, Peng, Xiaolin, Chen, Hongen, Dai, Shuhong, Ma, Wancheng, Wang, Changyi, Ma, Jianping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664794/
https://www.ncbi.nlm.nih.gov/pubmed/32358951
http://dx.doi.org/10.17305/bjbms.2020.4636
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author Xu, Shan
Shi, Qianping
Li, Bo
Han, Liyuan
Xu, Guodong
Peng, Xiaolin
Chen, Hongen
Dai, Shuhong
Ma, Wancheng
Wang, Changyi
Ma, Jianping
author_facet Xu, Shan
Shi, Qianping
Li, Bo
Han, Liyuan
Xu, Guodong
Peng, Xiaolin
Chen, Hongen
Dai, Shuhong
Ma, Wancheng
Wang, Changyi
Ma, Jianping
author_sort Xu, Shan
collection PubMed
description The MTHFR gene encodes methylenetetrahydrofolate reductase required for the metabolism of homocysteine (Hcy) – a previously reported independent risk factor for ischemic stroke (IS). In this study, we first aimed to clarify the association between DNA methylation levels in the MTHFR promoter and the risk of IS, followed by the analysis of potential interactions between environmental factors and DNA methylation levels that affect IS risk. We recruited 164 patients with hypertension and IS (case group) and 345 age-matched and sex-matched patients with hypertension only (control group). Demographic and clinical information was obtained using questionnaires, and blood samples were collected for biochemical analyses. Fluorescence quantitative methylation-specific PCR (qMSP) was used to detect MTHFR promoter methylation levels. A logistic regression analysis was performed to determine the relationship between environmental factors, MTHFR promoter methylation levels, and IS risk. We finally generated a receiver operating characteristic curve to determine whether MTHFR promoter methylation levels can predict IS. The mean MTHFR methylation levels in the case group (8.10 ± 6.14) were significantly lower than those in the control group (17.44 ± 3.16; p < 0.05). MTHFR promoter methylation levels were also lower in patients with plasma Hcy levels ≥15 μmol/L (10.65 ± 4.05) than in those with Hcy levels <15 μmol/L (16.74 ± 4.26, p < 0.001). Finally, we found that MTHFR hypermethylation is a protective factor for IS, particular in men (OR in men: 0.07; 95% CI: 0.02–0.16; p < 0.001). Further, sex and MTHFR promoter methylation levels exhibited a preliminary interaction effect on IS risk. These results indicate that MTHFR promoter methylation status might have diagnostic value in IS.
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spelling pubmed-76647942020-11-15 High MTHFR promoter methylation levels in men confer protection against ischemic stroke Xu, Shan Shi, Qianping Li, Bo Han, Liyuan Xu, Guodong Peng, Xiaolin Chen, Hongen Dai, Shuhong Ma, Wancheng Wang, Changyi Ma, Jianping Bosn J Basic Med Sci Research Article The MTHFR gene encodes methylenetetrahydrofolate reductase required for the metabolism of homocysteine (Hcy) – a previously reported independent risk factor for ischemic stroke (IS). In this study, we first aimed to clarify the association between DNA methylation levels in the MTHFR promoter and the risk of IS, followed by the analysis of potential interactions between environmental factors and DNA methylation levels that affect IS risk. We recruited 164 patients with hypertension and IS (case group) and 345 age-matched and sex-matched patients with hypertension only (control group). Demographic and clinical information was obtained using questionnaires, and blood samples were collected for biochemical analyses. Fluorescence quantitative methylation-specific PCR (qMSP) was used to detect MTHFR promoter methylation levels. A logistic regression analysis was performed to determine the relationship between environmental factors, MTHFR promoter methylation levels, and IS risk. We finally generated a receiver operating characteristic curve to determine whether MTHFR promoter methylation levels can predict IS. The mean MTHFR methylation levels in the case group (8.10 ± 6.14) were significantly lower than those in the control group (17.44 ± 3.16; p < 0.05). MTHFR promoter methylation levels were also lower in patients with plasma Hcy levels ≥15 μmol/L (10.65 ± 4.05) than in those with Hcy levels <15 μmol/L (16.74 ± 4.26, p < 0.001). Finally, we found that MTHFR hypermethylation is a protective factor for IS, particular in men (OR in men: 0.07; 95% CI: 0.02–0.16; p < 0.001). Further, sex and MTHFR promoter methylation levels exhibited a preliminary interaction effect on IS risk. These results indicate that MTHFR promoter methylation status might have diagnostic value in IS. Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina 2020-11 /pmc/articles/PMC7664794/ /pubmed/32358951 http://dx.doi.org/10.17305/bjbms.2020.4636 Text en Copyright: © The Author(s) (2020) http://creativecommons.org/licenses/by/4.0 This work is licensed under a Creative Commons Attribution 4.0 International License
spellingShingle Research Article
Xu, Shan
Shi, Qianping
Li, Bo
Han, Liyuan
Xu, Guodong
Peng, Xiaolin
Chen, Hongen
Dai, Shuhong
Ma, Wancheng
Wang, Changyi
Ma, Jianping
High MTHFR promoter methylation levels in men confer protection against ischemic stroke
title High MTHFR promoter methylation levels in men confer protection against ischemic stroke
title_full High MTHFR promoter methylation levels in men confer protection against ischemic stroke
title_fullStr High MTHFR promoter methylation levels in men confer protection against ischemic stroke
title_full_unstemmed High MTHFR promoter methylation levels in men confer protection against ischemic stroke
title_short High MTHFR promoter methylation levels in men confer protection against ischemic stroke
title_sort high mthfr promoter methylation levels in men confer protection against ischemic stroke
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664794/
https://www.ncbi.nlm.nih.gov/pubmed/32358951
http://dx.doi.org/10.17305/bjbms.2020.4636
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