The Glutamate Carboxypeptidase Gene II (C>T) Polymorphism Does Not Affect Folate Status in The Framingham Offspring Cohort

Abstract

Glutamate carboxypeptidase II (GCPII) hydrolyzes polyglutamyl folates before their absorption. 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. In this study, we examined the effect of this polymorphism in 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 probes. In the population as a whole, this mutation was not associated with lower plasma folate level or with elevated plasma homocysteine. In men, plasma folate concentrations were higher in carriers of the T allele compared with those homozygotes of the wild-type allele (P < 0.05), whereas in women folate concentrations did not differ between genotypes (P = 0.8). In its relationship to plasma folate, this mutation exhibited a weak interaction with age and gender only in older women (P = 0.05). Overall, our data show that the GCPII C1561T polymorphism is not a determinant of plasma folate or total homocysteine concentrations in this large cohort of participants from the Framingham Offspring Study.