Section of Clinical Pharmacology, Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
J Nutr. 2011 Oct;141(10):1784-90. doi: 10.3945/jn.111.141960. Epub 2011 Aug 24.
Two polymorphic variants in the gene coding for transcobalamin II (TCN2), TCN2 776C- > G and TCN2 67A- > G, may alter serum holotranscobalamin (holoTC), which in turn may affect cellular uptake of cobalamin (Cbl) and thereby Cbl status indicators. We studied the effects of TCN2 776C- > G and TCN2 67A- > G on blood concentrations of holoTC, Cbl, methylmalonic acid (MMA), and total homocysteine (tHcy) in 2411 individuals (50-64 y) that had been selected on the basis of these TCN2 genotypes from 10601 Norwegian inhabitants. The serum holoTC concentration was lower in TCN2 67AG (55 ± 0.75 pmol/L) and 67GG (48 ± 2.14 pmol/L) than in 67AA (62 ± 0.67 pmol/L) (P < 0.001) but did not differ among TCN2 776C- > G genotypes. The polymorphisms interacted as serum holoTC determinants (P = 0.001) and the presence of TCN2 67AG and GG in strata of 776CC and CG, but not 776GG, increased the risk of having serum holoTC < 45.6 pmol/L [tertile 1 vs. tertiles 2 and 3: OR = 2.5 (95% CI 1.8-3.5) for 67AG; OR = 5.7 (95% CI 3.5-9.1) for 67GG in 776CC; OR = 2.1 (95% CI 1.6-2.9) for 67AG; and OR = 4.5 (95% CI 2.4-8.2) for 67GG in 776CG; all P < 0.001]. Plasma MMA, tHcy, and Cbl were not affected by either polymorphism. In summary, serum holoTC, but not plasma Cbl, MMA, or tHcy, varied according to TCN2 67A- > G genotypes. It remains to be determined whether this polymorphic effect on serum holoTC alters its diagnostic utility as Cbl status indicator.
两种转钴胺素 II (TCN2) 基因编码的多态性变体，TCN2 776C- > G 和 TCN2 67A- > G，可能会改变血清全钴胺素 (holoTC)，而这反过来又可能影响钴胺素 (Cbl) 的细胞摄取，从而影响 Cbl 状态指标。我们研究了 TCN2 776C- > G 和 TCN2 67A- > G 对 2411 名个体（50-64 岁）血液中 holoTC、Cbl、甲基丙二酸 (MMA) 和总同型半胱氨酸 (tHcy) 浓度的影响，这些个体是根据这些 TCN2 基因型从 10601 名挪威居民中选择的。与 67AA（62 ± 0.67 pmol/L）相比，TCN2 67AG（55 ± 0.75 pmol/L）和 67GG（48 ± 2.14 pmol/L）的血清 holoTC 浓度较低（P < 0.001），但 TCN2 776C- > G 基因型之间无差异。这些多态性相互作用是血清 holoTC 的决定因素（P = 0.001），在 776CC 和 CG 层中存在 TCN2 67AG 和 GG，但不存在 776GG，增加了血清 holoTC < 45.6 pmol/L 的风险[第 1 三分位与第 2 和第 3 三分位相比：67AG 的 OR = 2.5（95%CI 1.8-3.5）；776CC 中 67GG 的 OR = 5.7（95%CI 3.5-9.1）；67AG 的 OR = 2.1（95%CI 1.6-2.9）；776CG 中 67GG 的 OR = 4.5（95%CI 2.4-8.2）；所有 P < 0.001]。血浆 MMA、tHcy 和 Cbl 不受任何一种多态性的影响。总之，血清 holoTC 而不是血浆 Cbl、MMA 或 tHcy 会根据 TCN2 67A- > G 基因型而变化。尚需确定这种对血清 holoTC 的多态性影响是否会改变其作为 Cbl 状态指标的诊断效用。
