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The association between MTHFR 677C>T genotype and folate status and genomic and gene-specific DNA methylation in the colon of individuals without colorectal neoplasia.
Am J Clin Nutr 2013; 98(6):1564-74AJ

Abstract

BACKGROUND

Decreased genomic and increased gene-specific DNA methylation predispose to colorectal cancer. Dietary folate intake and the methylenetetrahydrofolate reductase polymorphism (MTHFR 677C>T) may influence risk by modifying DNA methylation.

OBJECTIVE

We investigated the associations between MTHFR 677C>T genotype, folate status, and DNA methylation in the colon.

DESIGN

We conducted a cross-sectional study of 336 men and women (age 19-92 y) in the United Kingdom without colorectal neoplasia. We obtained blood samples for measurement of serum and red blood cell folate, plasma homocysteine, and MTHFR 677C>T genotype and colonic tissue biopsies for measurement of colonic tissue folate and DNA methylation (genomic- and gene-specific, estrogen receptor 1, ESR1; myoblast determination protein 1, MYOD1; insulin-like growth factor II, IGF2; tumor suppressor candidate 33, N33; adenomatous polyposis coli, APC; mut-L homolog 1, MLH1; and O(6)-methylguanine-DNA methyltransferase, MGMT) by liquid chromatography/electrospray ionization mass spectrometry and pyrosequencing, respectively.

RESULTS

Of the 336 subjects recruited, 185 (55%) carried the CC, 119 (35%) the CT, and 32 (10%) the TT alleles. No significant differences in systemic markers of folate status and colonic tissue folate between genotypes were found. The MTHFR TT genotype was not associated with genomic or gene-specific DNA methylation. Biomarkers of folate status were not associated with genomic DNA methylation. Relations between biomarkers of folate status and gene-specific methylation were inconsistent. However, low serum folate was associated with high MGMT methylation (P = 0.001).

CONCLUSION

MTHFR 677C>T genotype and folate status were generally not associated with DNA methylation in the colon of a folate-replete population without neoplasia.

Authors+Show Affiliations

Diabetes and Nutritional Sciences Division, King's College London, London, United Kingdom (J Hanks, IA, NK, AG, CLL, PE, and MP), and the Clinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom (CR, J Harris, and MP).No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24108782

Citation

Hanks, Joanna, et al. "The Association Between MTHFR 677C>T Genotype and Folate Status and Genomic and Gene-specific DNA Methylation in the Colon of Individuals Without Colorectal Neoplasia." The American Journal of Clinical Nutrition, vol. 98, no. 6, 2013, pp. 1564-74.
Hanks J, Ayed I, Kukreja N, et al. The association between MTHFR 677C>T genotype and folate status and genomic and gene-specific DNA methylation in the colon of individuals without colorectal neoplasia. Am J Clin Nutr. 2013;98(6):1564-74.
Hanks, J., Ayed, I., Kukreja, N., Rogers, C., Harris, J., Gheorghiu, A., ... Pufulete, M. (2013). The association between MTHFR 677C>T genotype and folate status and genomic and gene-specific DNA methylation in the colon of individuals without colorectal neoplasia. The American Journal of Clinical Nutrition, 98(6), pp. 1564-74. doi:10.3945/ajcn.113.061432.
Hanks J, et al. The Association Between MTHFR 677C>T Genotype and Folate Status and Genomic and Gene-specific DNA Methylation in the Colon of Individuals Without Colorectal Neoplasia. Am J Clin Nutr. 2013;98(6):1564-74. PubMed PMID: 24108782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The association between MTHFR 677C>T genotype and folate status and genomic and gene-specific DNA methylation in the colon of individuals without colorectal neoplasia. AU - Hanks,Joanna, AU - Ayed,Iyeman, AU - Kukreja,Neil, AU - Rogers,Chris, AU - Harris,Jessica, AU - Gheorghiu,Alina, AU - Liu,Chee Ling, AU - Emery,Peter, AU - Pufulete,Maria, Y1 - 2013/10/09/ PY - 2013/10/11/entrez PY - 2013/10/11/pubmed PY - 2014/4/8/medline SP - 1564 EP - 74 JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 98 IS - 6 N2 - BACKGROUND: Decreased genomic and increased gene-specific DNA methylation predispose to colorectal cancer. Dietary folate intake and the methylenetetrahydrofolate reductase polymorphism (MTHFR 677C>T) may influence risk by modifying DNA methylation. OBJECTIVE: We investigated the associations between MTHFR 677C>T genotype, folate status, and DNA methylation in the colon. DESIGN: We conducted a cross-sectional study of 336 men and women (age 19-92 y) in the United Kingdom without colorectal neoplasia. We obtained blood samples for measurement of serum and red blood cell folate, plasma homocysteine, and MTHFR 677C>T genotype and colonic tissue biopsies for measurement of colonic tissue folate and DNA methylation (genomic- and gene-specific, estrogen receptor 1, ESR1; myoblast determination protein 1, MYOD1; insulin-like growth factor II, IGF2; tumor suppressor candidate 33, N33; adenomatous polyposis coli, APC; mut-L homolog 1, MLH1; and O(6)-methylguanine-DNA methyltransferase, MGMT) by liquid chromatography/electrospray ionization mass spectrometry and pyrosequencing, respectively. RESULTS: Of the 336 subjects recruited, 185 (55%) carried the CC, 119 (35%) the CT, and 32 (10%) the TT alleles. No significant differences in systemic markers of folate status and colonic tissue folate between genotypes were found. The MTHFR TT genotype was not associated with genomic or gene-specific DNA methylation. Biomarkers of folate status were not associated with genomic DNA methylation. Relations between biomarkers of folate status and gene-specific methylation were inconsistent. However, low serum folate was associated with high MGMT methylation (P = 0.001). CONCLUSION: MTHFR 677C>T genotype and folate status were generally not associated with DNA methylation in the colon of a folate-replete population without neoplasia. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/24108782/The_association_between_MTHFR_677C>T_genotype_and_folate_status_and_genomic_and_gene_specific_DNA_methylation_in_the_colon_of_individuals_without_colorectal_neoplasia_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.3945/ajcn.113.061432 DB - PRIME DP - Unbound Medicine ER -