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Genetic variants of methionine metabolism and DNA methylation


Bleich, Stefan; Semmler, Alexander; Frieling, Helge; Thumfart, L; Muschler, Marc; Hillemacher, Thomas; Kornhuber, Johannes; Kallweit, Ulf; Simon, Matthias; Linnebank, Michael (2014). Genetic variants of methionine metabolism and DNA methylation. Epigenomics, 6(6):585-591.

Abstract

AIM: Altered DNA methylation is associated with important and common pathologies such as cancer. The origin of altered DNA methylation is unknown. The methyl groups for DNA methylation are provided by methionine metabolism. This metabolism is characterized by a high interindividual variability, which is in part explained by genetic variants.
METHODS: In a cohort of 313 individuals derived from a family-based study with index cases of cerebrovascular disease, we analyzed whether global methylation of leukocyte DNA was associated with age, gender, homocysteine plasma levels or functionally relevant genetic variants.
RESULTS: We observed an association of the G-allele of the methionine synthase variant c.2756A>G (D919G) with global methylation (% methylation ± 1 SD, AA: 41.3 ± 14.9; AG: 36.4 ± 18.2; GG: 30.8 ± 16.9; F = 4.799; p = 0.009). The methionine synthase variant c.2756A>G is associated with various types of cancer.
CONCLUSION: Our data suggest that an impact on DNA methylation may contribute to the clinical relevance of the methionine synthase variant.

AIM: Altered DNA methylation is associated with important and common pathologies such as cancer. The origin of altered DNA methylation is unknown. The methyl groups for DNA methylation are provided by methionine metabolism. This metabolism is characterized by a high interindividual variability, which is in part explained by genetic variants.
METHODS: In a cohort of 313 individuals derived from a family-based study with index cases of cerebrovascular disease, we analyzed whether global methylation of leukocyte DNA was associated with age, gender, homocysteine plasma levels or functionally relevant genetic variants.
RESULTS: We observed an association of the G-allele of the methionine synthase variant c.2756A>G (D919G) with global methylation (% methylation ± 1 SD, AA: 41.3 ± 14.9; AG: 36.4 ± 18.2; GG: 30.8 ± 16.9; F = 4.799; p = 0.009). The methionine synthase variant c.2756A>G is associated with various types of cancer.
CONCLUSION: Our data suggest that an impact on DNA methylation may contribute to the clinical relevance of the methionine synthase variant.

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2 citations in Scopus®
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Additional indexing

Item Type:Journal Article, not refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:German
Date:2014
Deposited On:04 Feb 2015 16:29
Last Modified:05 Apr 2016 18:48
Publisher:Future Medicine Ltd.
ISSN:1750-192X
Publisher DOI:https://doi.org/10.2217/epi.14.54
PubMed ID:25531253
Permanent URL: https://doi.org/10.5167/uzh-104646

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