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Int J Mol Epidemiol Genet 2012;3(2):160-173

Original Article
One-carbon metabolism nutrient status and plasma S-adenosylmethionine
concentrations in middle-aged and older Chinese in Singapore

Maki Inoue-Choi, Heather H. Nelson, Kim Robien, Erland Arning, Teodoro Bottiglieri, Woon-Puay Koh, Jian-Min Yuan

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota,
United States; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States; Institute of Metabolic
Disease, Baylor Research Institute, Dallas, Texas, USA; Saw Swee Hock School of Public Health, National University of
Singapore, Singapore; Present affiliation and address: Cancer Control and Population Sciences, University of Pittsburgh
Cancer Institute and Department of Epidemiology, University of Pittsburgh Graduate School of Public Health. Pittsburgh,
Pennsylvania, USA.

Received April 16, 2012; accepted May 13, 2012; Epub May 15, 2012; Published May 30, 2012

Abstract: S-adenosylmethionine (SAM) is a primary methyl donor for the methylation of many molecules including DNA. DNA
methylation is believed to play an important role in functions of cells and genes. Dietary, genetic and metabolic factors that
influence systematic SAM levels are not fully understood. We conducted cross-sectional analysis to evaluate associations
between plasma concentrations of one-carbon metabolism nutrients and metabolites and plasma SAM concentrations using
healthy individuals within the Singapore Chinese Health Study. Plasma SAM, betaine, choline, folate, total homocysteine (Hcy),
methionine, S-adenosylhomocysteine (SAH), vitamin B6 and vitamin B12 concentrations were quantified. Genotypes of
methionine adenosyltransferases (MAT1A, MAT2A and MAT2B) were also determined. Linear regression and path analysis
were performed to depict the directed dependencies in one-carbon metabolism. Age and body mass index were positively
associated while cigarette smoking were inversely associated with plasma SAM concentrations. Plasma choline, methionine
and SAH were positively and strongly associated with plasma SAM after adjustment for confounders. Plasma betaine and
folate were positively associated with plasma SAM only in men. Men carrying the variant MAT1A genotypes had lower plasma
SAM concentrations than men carrying the wild type genotype (p for gene x gender interaction = 0.02). This effect modification by
gender was restricted to individuals with low plasma methionine. In conclusion, plasma choline, methionine and SAH were
strongly associated with plasma SAM concentrations. The MAT1A genetic polymorphism may impact plasma SAM
concentrations in men with low plasma methionine concentrations. (IJMEG1204005).

Keywords: One-carbon metabolism, plasma SAM, MAT genetic polymorphism, path analysis

Address all correspondence to:
Dr. Maki Inoue-Choi
1300 S. Second Street, Suite 300
Minneapolis, MN 55454, USA.
Tel: +1 (612) 625-4542; Fax: +1 (612) 624-0315
E-mail: inou0021@umn.edu