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Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation.
Biochimie ( IF 3.3 ) Pub Date : 2020-04-21 , DOI: 10.1016/j.biochi.2020.04.004
Martina Rooney 1 , Teodoro Bottiglieri 2 , Brandi Wasek-Patterson 2 , Amy McMahon 1 , Catherine F Hughes 1 , Adrian McCann 3 , Geraldine Horigan 1 , J J Strain 1 , Helene McNulty 1 , Mary Ward 1
Affiliation  

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.

中文翻译:

MTHFR C677T多态性对一碳代谢产物的影响:核黄素补充的随机试验的证据。

MTHFR(TT基因型)中C677T多态性的纯合性与高血压风险增加24-87%相关。先前有报道称,TT基因型的成年人可通过补充MTHFR辅助因子核黄素来降低血压(BP)。与多态性相关的BP表型是否与扰动的一碳代谢有关。这项研究调查了具有TT基因型的成年人中的一碳代谢产物及其对核黄素的反应性。通过液相色谱法分析了以前参与RCT以降低BP的MTHFR基因型的成人血浆样本(115例),分析了蛋氨酸,S-腺苷甲硫氨酸(SAM),S-腺苷同型半胱氨酸(SAH),甜菜碱,胆碱和胱硫醚串联质谱(LC-MS / MS)。还研究了TT基因型成年人对核黄素(1.6 mg / d; n 24)或安慰剂(n 23)的单碳代谢产物反应16周。TT中血浆SAM(74.7±21.0 vs 85.2±22.6 nmol / L,P = 0.013)和SAM:SAH比(1.66±0.55 vs 1.85±0.51,P = 0.043)较低,血浆同型半胱氨酸较高(P = 0.043) ,与CC个人相比。对核黄素的反应,SAM(P = 0.008)和胱硫醚(P = 0.045)的浓度增加,而在其他一碳代谢产物中没有反应。这些发现证实了具有MTHFR 677TT基因型的个体的一碳代谢紊乱,并且首次证明在该基因型组中,SAM和胱硫醚对补充核黄素的反应增加。基因型特异的
更新日期:2020-04-22
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