THE GLUTAMATE CARBOXYPEPTIDASE GENE II (C>T) POLYMORPHISM DOES NOT AFFECT FOLATE STATUS IN THE FRAMINGHAM OFFSPRING COHORT

Authors: VARGAS-MARTINEZ, CAROLINA - HNRCA; ORDOVAS, JOSE - HNRCA; WILSON, PETER - BOSTON UNIVERSITY; SELHUB, JACOB - HNRCA

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/22/2002
Publication Date: 6/1/2002
Citation: Vargas-Martinez, C., Ordovas, J.M., Wilson, P.W., Selhub, J. 2002. The glutamate carboxypeptidase gene ii (c>t) polymorphism does not affect folate status in the framingham offspring cohort. Journal of Nutrition. 132(6):1176-9.

Interpretive Summary: Naturally occurring folates need to be hydrolyzed by the glutamate carboxypeptidase II (GCPII) in the small intestine in order to be absorbed. Recently, a mutation in the GCPII gene was reported to be associated with lower folate and higher homocysteine plasma concentrations in a small (n=75) selected elderly population. This would be as a result of impaired folate absorption resulting in reduced enzyme activity. The aim of the present study was to examine the effect of this mutation in GCPII in a large population-based cohort. We used cross-sectional information from 680 men and 644 women attending the fifth examination of the Framingham Offspring Study. We determined the different genotypes possible of the GCPII gene by allelic discrimination using Taqman(R) probes. Our data show that, in the population as a whole, this mutation is not associated with lower plasma folate level nor is it associated with elevated plasma homocysteine. In men, plasma folate concentrations were higher in carriers for the T allele compared to those homozygotes for the wild-type allele (P<0.05), whereas in women folate concentrations were not different between genotypes (P=0.8). We found that, in its relationship to plasma folate, this mutation exhibits a weak interaction with age and gender only in older women (P=0.05). We therefore conclude that in the Framingham Offspring Cohort the 1561 C>T mutation in GCPII has no consequences as far as folate and total homocysteine plasma levels are concerned.

Technical Abstract: Naturally occurring folates are comprised mostly of reduced polyglutamyl derivatives and require hydrolysis to monoglutamyl derivatives before they are absorbed by the small intestine. This hydrolysis is catalyzed by glutamate carboxypeptidase II (GCPII). Recently, a 1561 C>T polymorphism in the GCPII gene, was reported to be associated with lower folate and higher homocysteine plasma concentrations in a small (n=75) selected elderly population. It was postulated that this lower folate status was related to impaired folate absorption resulting in reduced enzyme activity induced by the mutation. The aim of this study was to examine the effect of this polymorphism in GCPII in a large population-based cohort. We used cross-sectional information from 680 men and 644 women attending the fifth examination of the Framingham Offspring Study. At the time of sample collection, subjects were not taking any supplements and were not exposed to food folate fortification. GCPII genotypes were determined by allelic discrimination using Taqman(R) probes. Our data show that, in the population as a whole, this mutation is not associated with lower plasma folate level nor is it associated with elevated plasma homocysteine. In men, plasma folate concentrations were higher in carriers for the T allele compared to those homozygotes for the wild-type allele (P<0.05), whereas in women folate concentrations were not different between genotypes (P=0.8). We found that, in its relationship to plasma folate, this mutation exhibits a weak interaction with age and gender only in older women (P=0.05).