Genetic determinants of the homocysteine level.
Elevated total homocysteine (tHcy) plasma concentrations indicate folate and/or vitamin B12 deficiency and are associated with cardiovascular disease and neural tube defects. Evidence has accumulated that folate-, vitamin B12-, and Hcy-metabolism are under genetic control. Because Hcy metabolism is impaired in renal failure, MTHFR 677 C>T, GCP2 1561C>T, RFC1 80G>A, and TCN2 776G>C may further aggravate hyperhomocysteinemia in these patients. The most consistent effect on tHcy plasma concentrations is observed for 677C>T of MTHFR, whereas GCP2, RFC1, and TCN2 polymorphisms show no major effect on tHcy concentrations. Much is yet to be learned about the impact of genetic variants on tHcy levels, human diseases, the genetic-nutrient interactions, as well as the pharmacogenetic consequences in Hcy and vitamin metabolism.
Sunder-Plassmann
Gere
G
Department of Medicine III, Division of Nephrology and Dialysis and Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Vienna, Austria. Gere.Sunder-Plassmann@univie.ac.at
Födinger
Manuela
M
D000954:Antigens, Surface; D002268:Carboxypeptidases / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D043425:Glutamate Carboxypeptidase II; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D014155:Transcobalamins / Q000235:genetics*
D000954:Antigens, Surface; D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C120043:SLC19A2 protein, human; D014155:Transcobalamins; D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002268:Carboxypeptidases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II