Folate network genetic variation, plasma homocysteine, and global genomic methylation content: a genetic association study

BMC Medical Genetics

Research Article

Patricia A Cassano¹  Valentina Bollati²  Scott T Weiss³  Augusto A Litonjua³  Martin T Wells⁴  Katherine L Tucker⁵  Andrew G Clark⁶  Joel Schwartz⁷  Andrea Baccarelli⁸  Patrick J Stover⁹  Susan M Wernimont⁹  J Michael Gaziano^1,10 

[1] 209 Savage Hall, Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA;Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Università degli Studi di Milano and IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy;Channing Laboratory, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA;Department of Biological Statistics & Computational Biology, Cornell, Ithaca, NY, USA;Department of Health Sciences, Northeastern University, Boston, MA, USA;Department of Molecular Biology & Genetics, Cornell University, Ithaca, NY, USA;Departments of Environmental Health and Epidemiology, Harvard University, Boston, MA, USA;Departments of Environmental Health and Epidemiology, Harvard University, Boston, MA, USA;Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Università degli Studi di Milano and IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy;Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA;Veterans Administration (VA) Normative Aging Study, VA Boston Healthcare System, and Division of Aging, Brigham & Women's Hospital, Boston, MA, USA;

关键词: Folate;    Homocysteine;    Plasma Homocysteine;    Folate Status;    Plasma Folate;   

DOI  :  10.1186/1471-2350-12-150

 received in 2011-05-27, accepted in 2011-11-21,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundSequence variants in genes functioning in folate-mediated one-carbon metabolism are hypothesized to lead to changes in levels of homocysteine and DNA methylation, which, in turn, are associated with risk of cardiovascular disease.Methods330 SNPs in 52 genes were studied in relation to plasma homocysteine and global genomic DNA methylation. SNPs were selected based on functional effects and gene coverage, and assays were completed on the Illumina Goldengate platform. Age-, smoking-, and nutrient-adjusted genotype--phenotype associations were estimated in regression models.ResultsUsing a nominal P ≤ 0.005 threshold for statistical significance, 20 SNPs were associated with plasma homocysteine, 8 with Alu methylation, and 1 with LINE-1 methylation. Using a more stringent false discovery rate threshold, SNPs in FTCD, SLC19A1, and SLC19A3 genes remained associated with plasma homocysteine. Gene by vitamin B-6 interactions were identified for both Alu and LINE-1 methylation, and epistatic interactions with the MTHFR rs1801133 SNP were identified for the plasma homocysteine phenotype. Pleiotropy involving the MTHFD1L and SARDH genes for both plasma homocysteine and Alu methylation phenotypes was identified.ConclusionsNo single gene was associated with all three phenotypes, and the set of the most statistically significant SNPs predictive of homocysteine or Alu or LINE-1 methylation was unique to each phenotype. Genetic variation in folate-mediated one-carbon metabolism, other than the well-known effects of the MTHFR c.665C>T (known as c.677 C>T, rs1801133, p.Ala222Val), is predictive of cardiovascular disease biomarkers.

【 授权许可】

Unknown   
© Wernimont et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.