ORCID: https://orcid.org/0000-0001-9084-7800; Uitterlinden, Andre G.; Greevenbroek, Marleen M. J. van
ORCID: https://orcid.org/0000-0002-2989-1631; Heemst, Diana van; Iterson, Maarten van; Wells, Philip S.; Yao, Chen; Deary, Ian J.; Gagnon, France; Heijmans, Bastiaan T.; Levy, Daniel; Morange, Pierre-Emmanuel; Waldenberger, Melanie; Heil, Sandra G. and Meurs, Joyce B. J. van
(2017):
Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes.
In: PLOS One
12(10), e0182472
[PDF, 1MB]

Abstract
Background DNA methylation is affected by the activities of the key enzymes and intermediate metabolites of the one-carbon pathway, one of which involves homocysteine. We investigated the effect of the well-known genetic variant associated with mildly elevated homocysteine: MTHFR 677C>T independently and in combination with other homocysteine-associated variants, on genome-wide leukocyte DNA-methylation. Methods Methylation levels were assessed using Illumina 450k arrays on 9,894 individuals of European ancestry from 12 cohort studies. Linear-mixed-models were used to study the association of additive MTHFR 677C> T and genetic-risk score (GRS) based on 18 homocysteineassociated SNPs, with genome-wide methylation. Results Meta-analysis revealed that the MTHFR 677C> T variant was associated with 35 CpG sites in cis, and the GRS showed association with 113 CpG sites near the homocysteine-associated variants. Genome-wide analysis revealed that the MTHFR 677C> T variant was associated with 1 trans-CpG (nearest gene ZNF184), while the GRS model showed association with 5 significant trans-CpGs annotated to nearest genes PTF1A, MRPL55, CTDSP2, CRYM and FKBP5. Conclusions Our results do not show widespread changes in DNA-methylation across the genome, and therefore do not support the hypothesis that mildly elevated homocysteine is associated with widespread methylation changes in leukocytes.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
URN: | urn:nbn:de:bvb:19-epub-51287-3 |
ISSN: | 1932-6203 |
Language: | English |
Item ID: | 51287 |
Date Deposited: | 14. Jun 2018, 09:45 |
Last Modified: | 09. Nov 2023, 12:20 |