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.
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.
Department of Pediatrics, PO Box 9101, University Medical Center Nijmegen, 6500 HB, Nijmegen, The Netherlands.
Karin J A
KJ
Lievers
Leo A J
LA
Kluijtmans
Godfried H J
GH
Boers
Petra
P
Verhoef
Martin
M
den Heijer
Frans J M
FJ
Trijbels
Henk J
HJ
Blom
D000328:Adult; D000704:Analysis of Variance; D000954:Antigens, Surface; D002268:Carboxypeptidases / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000097:blood*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D043425:Glutamate Carboxypeptidase II; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014805:Vitamin B 12 / Q000097:blood*
D000954:Antigens, Surface; D006710:Homocysteine; D005492:Folic Acid; D002268:Carboxypeptidases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D014805:Vitamin B 12