谷氨酸羧肽酶II基因不同基因型受试者中聚谷氨酸叶酸相对于单谷氨酸叶酸的生物利用度。

Bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid in subjects with different genotypes of the glutamate carboxypeptidase II gene.

作者信息

Melse-Boonstra Alida, Lievers Karin J A, Blom Henk J, Verhoef Petra

机构信息

Wageningen Centre for Food Sciences and the Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands.

出版信息

Am J Clin Nutr. 2004 Sep;80(3):700-4. doi: 10.1093/ajcn/80.3.700.

DOI:10.1093/ajcn/80.3.700

PMID:15321811

Abstract

BACKGROUND

Before dietary folate is absorbed, polyglutamate folates are deconjugated to monoglutamates by folylpoly-gamma-glutamyl carboxypeptidase in the small intestine. The 1561T allele of the glutamate carboxypeptidase II gene (GCPII), which codes for folylpoly-gamma-glutamyl carboxypeptidase, may impair intestinal absorption of dietary folates.

OBJECTIVE

Our aim was to study the bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid across GCPII 1561 genotypes.

DESIGN

In a randomized study, 180 healthy adults aged 50-75 y received 323 nmol monoglutamyl folic acid/d (n = 59), 262 nmol heptaglutamyl folic acid/d (n = 61), or placebo (n = 60) for 12 wk. Genotypes were assessed after the intervention. The bioavailability of heptaglutamyl folic acid relative to that of monoglutamyl folic acid was calculated by using the changes in serum folate concentration in the treatment groups, after correction for changes in the placebo group and for the administered dose.

RESULTS

No subjects with the TT genotype were encountered. At baseline, serum and erythrocyte folate concentrations were higher (P < 0.05) in subjects with the CT genotype [16.3 nmol/L (geometric x; 95% CI: 13.7, 19.3 nmol/L) and 863 nmol/L (735, 1012 nmol/L), respectively; n = 19] than in subjects with the CC genotype [13.7 (13.1, 14.3) and 685 (652, 721) nmol/L, respectively; n = 161]. Baseline homocysteine concentrations were not significantly different between genotypes. The bioavailability of heptaglutamyl folic acid relative to that of monoglutamyl folic acid was not significantly different between subjects with the CC (64%; 52%, 76%) and CT genotypes (70%; 49%, 91%).

CONCLUSIONS

The 1561T allele of the GCPII gene does not impair the bioavailability of polyglutamyl folic acid. However, the allele is associated with higher folate status. This association may be explained by yet unidentified factors controlling the expression of the GCPII gene.

摘要

背景

膳食叶酸被吸收之前，小肠中的叶酰聚 -γ- 谷氨酰羧肽酶会将多聚谷氨酸叶酸解聚为单谷氨酸叶酸。编码叶酰聚 -γ- 谷氨酰羧肽酶的谷氨酸羧肽酶 II 基因（GCPII）的 1561T 等位基因可能会损害膳食叶酸的肠道吸收。

目的

我们的目的是研究跨 GCPII 1561 基因型的多聚谷氨酸叶酸相对于单谷氨酸叶酸的生物利用度。

设计

在一项随机研究中，180 名年龄在 50 - 75 岁的健康成年人接受了为期 12 周的每日 323 nmol 单谷氨酸叶酸（n = 59）、每日 262 nmol 七聚谷氨酸叶酸（n = 61）或安慰剂（n = 60）。干预后评估基因型。通过校正安慰剂组的变化和给药剂量后，利用治疗组血清叶酸浓度的变化来计算七聚谷氨酸叶酸相对于单谷氨酸叶酸的生物利用度。

结果

未遇到 TT 基因型的受试者。基线时，CT 基因型受试者的血清和红细胞叶酸浓度较高（P < 0.05）[分别为 16.3 nmol/L（几何均值；95% CI：13.7，19.3 nmol/L）和 863 nmol/L（735，1012 nmol/L）；n = 19]，高于 CC 基因型受试者[分别为 13.7（13.1，14.3）和 685（652，721）nmol/L；n = 161]。不同基因型之间的基线同型半胱氨酸浓度无显著差异。CC 基因型（64%；52%，76%）和 CT 基因型受试者（70%；49%，91%）之间，七聚谷氨酸叶酸相对于单谷氨酸叶酸的生物利用度无显著差异。