Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6084, USA.
Eur J Clin Nutr. 2010 Nov;64(11):1338-43. doi: 10.1038/ejcn.2010.157. Epub 2010 Sep 1.
BACKGROUND/OBJECTIVES: Methionine synthase catalyzes the conversion of 5-methyltetrahydrofolate to tetrahydrofolate and homocysteine (Hcy) to methionine using vitamin B(12) as a cofactor. Transcobalamin is the main transporter of vitamin B(12) from blood into cells. This study was undertaken to assess the relationship between the transcobalamin P259R (TCN2 776C>G) polymorphism and both serum vitamin B(12) and total Hcy (tHcy) levels.
SUBJECTS/METHODS: The population comprised 613 men from Northern Ireland, aged 30-49 years, for whom tHcy, serum vitamin B(12) and serum folate concentrations were available. TCN2 776C>G genotypes were determined using a TaqMan 5' nuclease Real-Time PCR assay. Standard statistical tests of association were applied to assess the relationships between the polymorphism and phenotypic variables.
The TCN2 776CC homozygous genotype was associated with lower serum vitamin B(12) concentrations compared with the 776CG (P(unadjusted)=0.01; P(adjusted)=0.03) and 776GG genotypes (P(unadjusted)=0.015; P(adjusted)=0.045). Among individuals with vitamin B(12) concentrations in the lower half of the distribution, tHcy concentrations were higher in TCN2 776GG homozygotes than in individuals with the other genotypes (P(unadjusted)=0.015; P(adjusted)=0.06).
These data suggest that, relative to transcobalamin with arginine at position 259 (776G), transcobalamin with proline at this position (776C) is either more efficient at vitamin B(12) transport from blood to tissues or has higher affinity for vitamin B(12). Furthermore, vitamin B(12) status influences the relationship between TCN2 776C>G genotype and tHcy concentrations. Thus, the TCN2 776C>G polymorphism may contribute to the risk of pathologies associated with a low B(12), and high tHcy phenotype.
背景/目的：蛋氨酸合成酶以维生素 B12 为辅因子将 5-甲基四氢叶酸转化为四氢叶酸，将同型半胱氨酸（Hcy）转化为蛋氨酸。转钴胺素是维生素 B12 从血液进入细胞的主要转运蛋白。本研究旨在评估转钴胺素 P259R（TCN2 776C>G）多态性与血清维生素 B12 和总 Hcy（tHcy）水平之间的关系。
受试者/方法：该人群包括来自北爱尔兰的 613 名 30-49 岁男性，他们的 tHcy、血清维生素 B12 和血清叶酸浓度可用。使用 TaqMan 5' 核酸酶实时 PCR 检测法确定 TCN2 776C>G 基因型。应用标准关联统计检验评估多态性与表型变量之间的关系。
与 776CG（未调整 P=0.01；调整后 P=0.03）和 776GG 基因型相比，TCN2 776CC 纯合基因型与较低的血清维生素 B12 浓度相关（未调整 P=0.01；调整后 P=0.045）。在维生素 B12 浓度处于分布较低一半的个体中，TCN2 776GG 纯合子的 Hcy 浓度高于其他基因型（未调整 P=0.015；调整后 P=0.06）。
这些数据表明，与位置 259 处为精氨酸的转钴胺素（776G）相比，位置 259 处为脯氨酸的转钴胺素（776C）在从血液向组织转运维生素 B12 方面更有效，或者对维生素 B12 具有更高的亲和力。此外，维生素 B12 状态影响 TCN2 776C>G 基因型与 tHcy 浓度之间的关系。因此，TCN2 776C>G 多态性可能导致与低 B12 和高 tHcy 表型相关的病理风险增加。
