Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Cromore Rd, Coleraine, BT52 1SA, Northern Ireland, UK.
Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott & White Research Institute, 3812 Elm St, Dallas, TX, 75226, USA.
Biochimie. 2020 Jun;173:91-99. doi: 10.1016/j.biochi.2020.04.004. Epub 2020 Apr 21.
Homozygosity for the C677T polymorphism in MTHFR (TT genotype) is associated with a 24-87% increased risk of hypertension. Blood pressure (BP) lowering was previously reported in adults with the TT genotype, in response to supplementation with the MTHFR cofactor, riboflavin. Whether the BP phenotype associated with the polymorphism is related to perturbed one-carbon metabolism is unknown. This study investigated one-carbon metabolites and their responsiveness to riboflavin in adults with the TT genotype. Plasma samples from adults (n 115) screened for the MTHFR genotype, who previously participated in RCTs to lower BP, were analysed for methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), betaine, choline and cystathionine by liquid chromatography tandem mass spectrometry (LC-MS/MS). The one-carbon metabolite response to riboflavin (1.6 mg/d; n 24) or placebo (n 23) for 16 weeks in adults with the TT genotype was also investigated. Plasma SAM (74.7 ± 21.0 vs 85.2 ± 22.6 nmol/L, P = 0.013) and SAM:SAH ratio (1.66 ± 0.55 vs 1.85 ± 0.51, P = 0.043) were lower and plasma homocysteine was higher (P = 0.043) in TT, compared to CC individuals. In response to riboflavin, SAM (P = 0.008) and cystathionine (P = 0.045) concentrations increased, with no responses in other one-carbon metabolites observed. These findings confirm perturbed one-carbon metabolism in individuals with the MTHFR 677TT genotype, and for the first time demonstrate that SAM, and cystathionine, increase in response to riboflavin supplementation in this genotype group. The genotype-specific, one-carbon metabolite responses to riboflavin intervention observed could offer some insight into the role of this gene-nutrient interaction in blood pressure.
亚甲基四氢叶酸还原酶（MTHFR）C677T 多态性纯合子（TT 基因型）与高血压风险增加 24%-87%相关。先前有研究报道，TT 基因型的成年人在补充 MTHFR 辅助因子——核黄素后，血压会降低。但目前尚不清楚与该多态性相关的血压表型是否与一碳代谢紊乱有关。本研究旨在探讨 TT 基因型成年人的一碳代谢物及其对核黄素的反应性。本研究对先前参与降低血压随机对照试验的成年人进行了 MTHFR 基因型筛查，分析了他们的血浆样本中的蛋氨酸、S-腺苷甲硫氨酸（SAM）、S-腺苷同型半胱氨酸（SAH）、甜菜碱、胆碱和胱硫醚，采用液相色谱串联质谱法（LC-MS/MS）进行分析。本研究还探讨了 TT 基因型成年人在接受核黄素（1.6mg/d；n=24）或安慰剂（n=23）治疗 16 周后的一碳代谢物反应。与 CC 个体相比，TT 个体的血浆 SAM（74.7±21.0 与 85.2±22.6 nmol/L，P=0.013）和 SAM:SAH 比值（1.66±0.55 与 1.85±0.51，P=0.043）较低，血浆同型半胱氨酸水平较高（P=0.043）。对核黄素的反应中，SAM（P=0.008）和胱硫醚（P=0.045）浓度增加，而其他一碳代谢物未观察到反应。这些发现证实了 MTHFR 677TT 基因型个体的一碳代谢紊乱，并且首次证明了 SAM 和胱硫醚在该基因型组中对核黄素补充有反应。本研究首次观察到 MTHFR 基因-营养素相互作用在 TT 基因型人群中对核黄素干预的特定一碳代谢物反应，这为该基因-营养素相互作用在血压中的作用提供了一些见解。
