Gene expression profiles of the one-carbon metabolism pathway

Yin Leng Lee; Xinran Xu; Sylvan Wallenstein; Jia Chen

doi:10.1016/S1673-8527(08)60115-0

Volume 36 Issue 5

May 2009

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Article Navigation > Journal of Genetics and Genomics > 2009 > 36(5): 277-282

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Gene expression profiles of the one-carbon metabolism pathway

doi: 10.1016/S1673-8527(08)60115-0

Yin Leng Lee^{a, b, #},
Xinran Xu^{a, #},
Sylvan Wallenstein^a,
Jia Chen^{a, c, d}

a
Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York 10029, USA
b
Department of Microbiology, Mount Sinai School of Medicine, New York 10029, USA
c
Department of Pediatrics, Mount Sinai School of Medicine, New York 10029, USA
d
Department of Oncological Science, Mount Sinai School of Medicine, New York 10029, USA

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Corresponding author: E-mail address: jia.chen@mssm.edu (Jia Chen)
Received Date: 2008-11-03
Accepted Date: 2009-01-20
Rev Recd Date: 2008-12-24

Available Online: 2009-05-15

Publish Date: 2009-05-20

Abstract

Abstract

One-carbon metabolism plays a critical role in both DNA methylation and DNA synthesis. Accumulating evidence has shown that interruptions of this pathway are associated with many disease outcomes including cardiovascular diseases and cancers. Mechanistic studies have been performed on genetic polymorphisms involved in one-carbon metabolism. However, expression profiles of these inter-related genes are not well-known. In this study, we examined the gene expression profiles of 11 one-carbon metabolizing genes by quantifying the mRNA level of the lymphocyte among 54 healthy individuals and explored the correlations of these genes. We found these genes were expressed in lymphocytes at moderate levels and showed significant inter-person variations. We also applied principle component analysis to explore potential patterns of expression. The components identified by the program agreed with existing knowledge about one-carbon metabolism. This study helps us better understand the biological functions of one-carbon metabolism.
- one-carbon metabolism,
- expression,
- principle component analysis (PCA)

These authors contributed equally to this work.

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References(23)

References

[1]	Appling, D. Compartmentation of folate-mediated one-carbon metabolism in eukaryotes FASEB J., 5 (1991),pp. 2645-2651
[2]	Bagnyukova, T.V., Powell, C.L., Pavliv, O. et al. Induction of oxidative stress and DNA damage in rat brain by a folate/methyl-deficient diet Brain Res., 1237 (2008),pp. 44-51
[3]	Bailey, L.B., Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: Metabolic significance, risks and impact on folate requirement J. Nutr., 129 (1999),pp. 919-922
[4]	Beaudin, A.E., Stover, P.J. Folate-mediated one-carbon metabolism and neural tube defects: Balancing genome synthesis and gene expression Birth Defects Res. C Embryo Today, 81 (2007),pp. 183-203
[5]	Blount, B.C., Mack, M.M., Wehr, C.M. et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: Implications for cancer and neuronal damage Proc. Natl. Acad. Sci. USA, 94 (1997),pp. 3290-3295
[6]	Bustin, S.A. Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays J. Mol. Endocrinol., 25 (2000),pp. 169-193
[7]	Celtikci, B., Leclerc, D., Lawrance, A.K. et al. Altered expression of methylenetetrahydrofolate reductase modifies response to methotrexate in mice Pharmacogenet. Genomics, 18 (2008),pp. 577-589
[8]	Chen, X., Wang, L., Smith, J.D. et al. Supervised principal component analysis for gene set enrichment of microarray data with continuous or survival outcomes Bioinformatics, 24 (2008),pp. 2474-2481
[9]	Frosst, P., Blom, H.J., Milos, R. et al. A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase Nat. Genet., 10 (1995),pp. 111-113
[10]	Hoffman, D., Marion, D., Cornatzer, W. et al. S-adenosylmethionine and S-adenosylhomocystein metabolism in isolated rat liver. Effects of L-methionine, L-homocystein, and adenosine J. Biol. Chem., 255 (1980),pp. 10822-10827
[11]	Jencks, D., Mathews, R. Allosteric inhibition of methylenetetrahydrofolate reductase by adenosylmethionine. Effects of adenosylmethionine and NADPH on the equilibrium between active and inactive forms of the enzyme and on the kinetics of approach to equilibrium J. Biol. Chem., 262 (1987),pp. 2485-2493
[12]	Livak, K.J., Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method Methods, 25 (2001),pp. 402-408
[13]	Machlin, L.J.
[14]	Reed, M.C., Nijhout, H.F., Neuhouser, M.L. et al. A mathematical model gives insights into nutritional and genetic aspects of folate-mediated one-carbon metabolism J. Nutr., 136 (2006),pp. 2653-2661
[15]	Ringner, M. What is principal component analysis? Nat. Biotechnol., 26 (2008),pp. 303-304
[16]	Shane, B. Folylpolyglutamate synthesis and role in the regulation of one-carbon metabolism Vitam. Horm., 45 (1989),pp. 263-335
[17]	Slopien, R., Jasniewicz, K., Meczekalski, B. et al. Maturitas, 61 (2008),pp. 252-255
[18]	Song, J.H., Kim, H.J., Lee, C.H. et al. Identification of gene expression signatures for molecular classification in human leukemia cells Int. J. Oncol., 29 (2006),pp. 57-64
[19]	Stern, L.L., Mason, J.B., Selhub, J. et al. Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene Cancer Epidemiol. Biomarkers Prev., 9 (2000),pp. 849-853
[20]	Suzuki, T., Matsuo, K., Sawaki, A. et al. Alcohol drinking and one-carbon metabolism-related gene polymorphisms on pancreatic cancer risk Cancer Epidemiol. Biomarkers Prev., 17 (2008),pp. 2742-2747
[21]	Ulrich, C.M., Nijhout, H.F., Reed, M.C. Mathematical modeling: Epidemiology meets systems biology Cancer Epidemiol. Biomarkers Prev., 15 (2006),pp. 827-829
[22]	Ulvik, A., Ueland, P.M., Fredriksen, A. et al. Functional inference of the methylenetetrahydrofolate reductase 677C > T and 1298A > C polymorphisms from a large-scale epidemiological study Hum. Genet., 121 (2007),pp. 57-64
[23]	Xu, X., Chen, J. One-carbon metabolism and breast cancer: An epidemiological perspectine J. Genet. Genomics, 36 (2009),pp. 203-214