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Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults.
Blood 2003; 101(7):2483-8Blood

Abstract

A modestly elevated total plasma homocysteine concentration (tHcy) is generally accepted as an independent and graded risk factor for various pathologies, including vascular diseases, neural tube defects, Alzheimer disease, and pregnancy complications. We analyzed 5 common functional polymorphisms in enzymes involved in homocysteine metabolism (ie, methylenetetrahydrofolate reductase [MTHFR] 677C>T and 1298A>C, methionine synthase [MTR] 2756A>G, cystathionine beta-synthase [CBS] 844ins68, and methionine synthase reductase [MTRR] 66A>G) in 452 young adults, and quantified their independent and interactive effects on tHcy concentrations. Serum folate, red cell folate, vitamin B(12), and tHcy concentrations were significantly influenced by MTHFR 677C>T genotypes. A particularly strong interaction was observed between the MTHFR 677TT genotype and serum folate, which led to a high tHcy phenotype that was more pronounced in males. The genetic contribution to the variance in tHcy was estimated to be approximately 9%, compared with approximately 35% that could be attributed to low folate and vitamin B(12). Our study indicates that dietary factors are centrally important in the control of tHcy levels in young adults with additional, but somewhat weaker, genetic effects. These data underscore the potential benefits that may be gained by improving the dietary status of young adults, and provide support for the implementation of folate/B-vitamin food fortification programs.

Authors+Show Affiliations

Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.No affiliation info availableNo 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)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12642343

Citation

Kluijtmans, Leo A J., et al. "Genetic and Nutritional Factors Contributing to Hyperhomocysteinemia in Young Adults." Blood, vol. 101, no. 7, 2003, pp. 2483-8.
Kluijtmans LA, Young IS, Boreham CA, et al. Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults. Blood. 2003;101(7):2483-8.
Kluijtmans, L. A., Young, I. S., Boreham, C. A., Murray, L., McMaster, D., McNulty, H., ... Whitehead, A. S. (2003). Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults. Blood, 101(7), pp. 2483-8.
Kluijtmans LA, et al. Genetic and Nutritional Factors Contributing to Hyperhomocysteinemia in Young Adults. Blood. 2003 Apr 1;101(7):2483-8. PubMed PMID: 12642343.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults. AU - Kluijtmans,Leo A J, AU - Young,Ian S, AU - Boreham,Colin A, AU - Murray,Liam, AU - McMaster,Dorothy, AU - McNulty,Helene, AU - Strain,J J, AU - McPartlin,Joseph, AU - Scott,John M, AU - Whitehead,Alexander S, PY - 2003/3/19/pubmed PY - 2003/5/22/medline PY - 2003/3/19/entrez SP - 2483 EP - 8 JF - Blood JO - Blood VL - 101 IS - 7 N2 - A modestly elevated total plasma homocysteine concentration (tHcy) is generally accepted as an independent and graded risk factor for various pathologies, including vascular diseases, neural tube defects, Alzheimer disease, and pregnancy complications. We analyzed 5 common functional polymorphisms in enzymes involved in homocysteine metabolism (ie, methylenetetrahydrofolate reductase [MTHFR] 677C>T and 1298A>C, methionine synthase [MTR] 2756A>G, cystathionine beta-synthase [CBS] 844ins68, and methionine synthase reductase [MTRR] 66A>G) in 452 young adults, and quantified their independent and interactive effects on tHcy concentrations. Serum folate, red cell folate, vitamin B(12), and tHcy concentrations were significantly influenced by MTHFR 677C>T genotypes. A particularly strong interaction was observed between the MTHFR 677TT genotype and serum folate, which led to a high tHcy phenotype that was more pronounced in males. The genetic contribution to the variance in tHcy was estimated to be approximately 9%, compared with approximately 35% that could be attributed to low folate and vitamin B(12). Our study indicates that dietary factors are centrally important in the control of tHcy levels in young adults with additional, but somewhat weaker, genetic effects. These data underscore the potential benefits that may be gained by improving the dietary status of young adults, and provide support for the implementation of folate/B-vitamin food fortification programs. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/12642343/Genetic_and_nutritional_factors_contributing_to_hyperhomocysteinemia_in_young_adults_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=12642343 DB - PRIME DP - Unbound Medicine ER -