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Influence of a glutamate carboxypeptidase II (GCPII) polymorphism (1561C-->T) on plasma homocysteine, folate and vitamin B(12) levels and its relationship to cardiovascular disease risk.

Abstract
Elevated levels of total homocysteine and low folate in blood are independent and graded risk factors for arterial occlusive disease. An impairment of folate distribution can be an important cause of hyperhomocysteinemia. Glutamate carboxypeptidase II (GCPII) regulates the absorption of dietary folates. In the present study, we examined the relationship of a 1561C-->T variant in the GCPII gene with fasting, post-methionine load plasma homocysteine, folate and vitamin B(12) levels and the risk of cardiovascular disease (CVD) in 190 vascular disease patients and in 601 apparently healthy controls. Fasting as well as post-load homocysteine concentrations associated with the 1561TT genotype tended to be lower, whereas the homocysteine concentrations of the 1561CT individuals were not different from their 1561CC peers. The 1561C-->T polymorphism significantly increased both red blood cell folate and plasma folate concentrations (ANOVA P=0.013; test for linear trend P=0.03, respectively), but had no effect on vitamin B(12) levels (ANOVA P=0.35). Since not only homocysteine itself is considered to be positively associated with the risk of CVD, but also a decreased folate status, the results of this study indicate that the 1561C-->T polymorphism may affect the predisposition to CVD.
AuthorsKarin J A Lievers, Leo A J Kluijtmans, Godfried H J Boers, Petra Verhoef, Martin den Heijer, Frans J M Trijbels, Henk J Blom
JournalAtherosclerosis (Atherosclerosis) Vol. 164 Issue 2 Pg. 269-73 (Oct 2002) ISSN: 0021-9150 [Print] Ireland
PMID12204797 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Surface
  • Homocysteine
  • Folic Acid
  • Carboxypeptidases
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Vitamin B 12
Topics
  • Adult
  • Analysis of Variance
  • Antigens, Surface
  • Carboxypeptidases (genetics)
  • Cardiovascular Diseases (genetics, metabolism)
  • Case-Control Studies
  • Female
  • Folic Acid (blood)
  • Genetic Predisposition to Disease
  • Genotype
  • Glutamate Carboxypeptidase II
  • Homocysteine (blood)
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Genetic
  • Probability
  • Reference Values
  • Risk Assessment
  • Sensitivity and Specificity
  • Vitamin B 12 (blood)

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