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Plasma S-adenosylmethionine, DNMT polymorphisms, and peripheral blood LINE-1 methylation among healthy Chinese adults in Singapore

Inoue-Choi, M and Nelson, HH and Robien, K and Arning, E and Bottiglieri, T and Koh, WP and Yuan, JM (2013) Plasma S-adenosylmethionine, DNMT polymorphisms, and peripheral blood LINE-1 methylation among healthy Chinese adults in Singapore. BMC Cancer, 13.

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Abstract

Background: Global hypomethylation of repetitive DNA sequences is believed to occur early in tumorigenesis. There is a great interest in identifying factors that contribute to global DNA hypomethylation and associated cancer risk. We tested the hypothesis that plasma S-adenosylmethionine (SAM) level alone or in combination with genetic variation in DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) was associated with global DNA methylation extent at long interspersed nucleotide element-1 (LINE-1) sequences.Methods: Plasma SAM level and LINE-1 DNA methylation index were measured using stored blood samples collected from 440 healthy Singaporean Chinese adults during 1994-1999. Genetic polymorphisms of 13 loci in DNMT1, DNMT3A and DNMT3B were determined.Results: LINE-1 methylation index was significantly higher in men than in women (p = 0.001). LINE-1 methylation index was positively associated with plasma SAM levels (p ≤ 0.01), with a plateau at approximately 78% of LINE-1 methylation index (55 nmol/L plasma SAM) in men and 77% methylation index (50 nmol/L plasma SAM) in women. In men only, the T allele of DNMT1 rs21124724 was associated with a statistically significantly higher LINE-1 methylation index (ptrend = 0.001). The DNMT1 rs2114724 genotype modified the association between plasma SAM and LINE-1 methylation index at low levels of plasma SAM in men.Conclusions: Circulating SAM level was associated with LINE-1 methylation status among healthy Chinese adults. The DNMT1 genetic polymorphism may exert a modifying effect on the association between SAM and LINE-1 methylation status in men, especially when plasma SAM level is low. Our findings support a link between plasma SAM and global DNA methylation status at LINE-1 sequences. © 2013 Inoue-Choi et al.; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Inoue-Choi, M
Nelson, HH
Robien, K
Arning, E
Bottiglieri, T
Koh, WP
Yuan, JMyuanj@pitt.eduYUANJ
Centers: Other Centers, Institutes, or Units > Pittsburgh Cancer Institute
Date: 17 August 2013
Date Type: Publication
Journal or Publication Title: BMC Cancer
Volume: 13
DOI or Unique Handle: 10.1186/1471-2407-13-389
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
Date Deposited: 02 Dec 2016 14:58
Last Modified: 20 Mar 2019 08:55
URI: http://d-scholarship.pitt.edu/id/eprint/29693

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