Kimura H, Gejyo F, Suzuki S, Takeda T, Miyazaki R, Yoshida H
Department of Clinical Laboratory Medicine and Nephrology, Faculty of Medicine, Fukui Medical University, Niigata, Japan.
Am J Kidney Dis. 2000 Nov;36(5):925-33. doi: 10.1053/ajkd.2000.19085.
Patients undergoing hemodialysis have impaired metabolism of such sulfur-containing amino acids as cysteine (Cys) and homocysteine (Hcy), which may lead to accelerated atherosclerosis. Considering that Cys is mainly synthesized from Hcy, a common C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene may affect the serum total Cys (tCys) concentration, as well as total Hcy (tHcy) concentration, through reduced remethylation of Hcy to methionine, even in hemodialysis patients. To identify the independent determinants for the tCys concentration in dialysis patients, we determined MTHFR C/T genotypes and serum concentrations of tHcy, tCys, and vitamins as cofactors in 464 hemodialysis patients. Serum tCys concentration was positively associated with serum tHcy concentration and negatively associated with the MTHFR mutation, although the mutation correlated positively with serum tHcy concentration. Slopes of regression lines relating tHcy and tCys concentrations differed between the MTHFR genotypes, and the relationship was strengthened with a decreasing number of T alleles. Additionally, serum concentrations of folate and vitamin B(12) correlated positively with tCys concentration, whereas they correlated negatively with tHcy concentration. These findings suggest that the MTHFR mutation is an independent predictor for serum tCys concentrations in hemodialysis patients and that a tCys-decreasing effect of the mutation may arise largely from its attenuation of the positive Cys-Hcy correlation. The tCys-increasing effect of folate and vitamin B(12) appears to be linked to their enhancement of Hcy remethylation.
接受血液透析的患者，其半胱氨酸（Cys）和同型半胱氨酸（Hcy）等含硫氨基酸的代谢受损，这可能会导致动脉粥样硬化加速。鉴于Cys主要由Hcy合成，即使在血液透析患者中，亚甲基四氢叶酸还原酶（MTHFR）基因常见的C677T突变也可能通过减少Hcy再甲基化为蛋氨酸，影响血清总半胱氨酸（tCys）浓度以及总同型半胱氨酸（tHcy）浓度。为了确定透析患者tCys浓度的独立决定因素，我们测定了464例血液透析患者的MTHFR C/T基因型以及tHcy、tCys的血清浓度和作为辅助因子的维生素。血清tCys浓度与血清tHcy浓度呈正相关，与MTHFR突变呈负相关，尽管该突变与血清tHcy浓度呈正相关。MTHFR基因型之间，tHcy和tCys浓度回归线的斜率不同，且随着T等位基因数量的减少，这种关系增强。此外，叶酸和维生素B12的血清浓度与tCys浓度呈正相关，而与tHcy浓度呈负相关。这些发现表明，MTHFR突变是血液透析患者血清tCys浓度的独立预测因子，该突变降低tCys的作用可能主要源于其减弱了Cys-Hcy的正相关关系。叶酸和维生素B12升高tCys的作用似乎与其增强Hcy再甲基化有关。
