Siddiqi Sultan Mehmood, Liu Lishun, Du Yiming, Song Yun, Chen Ping, Li Shuqun, He Qiangqiang, Zhou Ziyi, Xu Jiafeng, Bai Jie, Wang Binyan, Qin Xianhui, Mehmood Anam, Xiuqing Liu, Cheng Xiaoxu, Shi Han-Ping
Graduate School at Shenzhen, Tsinghua University, Shenzhen, China.
Graduate School at Shenzhen, Tsinghua University, Shenzhen, China; Guangdong Key Laboratory of H-type Hypertension and Stroke Precision Prevention Research and Development Enterprise, Shenzhen AUSA Pharmaceutical Co. Ltd, Shenzhen, China.
J Nutr. 2025 Apr;155(4):1202-1209. doi: 10.1016/j.tjnut.2024.09.003. Epub 2024 Sep 18.
In China, the MTHFR 677T allele, unlike in most Western populations, is a rare genetic variant linked to various disorders. The contributing nutritional and genetic factors to this genetic risk remain unclear.
This study aimed to elucidate the interactions between genetic variations in total homocysteine (tHcy) pathway genes, serum tHcy concentrations, and nutritional factors in a Chinese population with hypertension.
This study analyzed 1304 Chinese adults with hypertension aged ≥18 y enrolled in the China Precision Nutrition and Health KAP Real World Study (CPNAS). Serum concentrations of vitamin B12 and folate were measured using the magnetic microparticle chemiluminescence method, and tHcy concentrations were measured using Hcy Assay kits. Identification of the MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms was performed via time-of-flight nucleic spectrometry.
Our findings revealed significant sex differences in tHcy concentrations, with males exhibiting higher tHcy concentrations than females (13.95 μmol/L vs. 11.15 μmol/L, P < 0.001). Individuals deficient in both vitamin B12 and folate had an increased risk of hyperhomocysteinemia (H-Hcy) (57.4%). In contrast, the prevalence of H-Hcy was lower among those deficient in either vitamin B12 (31.1%) or folate (23.2%) alone. Significant associations were identified between the MTHFR C677T and A1298C polymorphisms and elevated serum tHcy concentrations, particularly in individuals homozygous for the T allele. Conversely, the MTRR A66G genotype did not show a significant correlation with tHcy concentrations. Optimal vitamin B12 concentrations significantly modulated the genotypic effect on tHcy concentrations, with individuals having adequate vitamin B12 and folate exhibiting low tHcy concentrations, even among high-risk genotypes (TT).
Adequate concentrations of folate and vitamin B12 significantly reduce serum tHcy concentrations and mitigate the genotypic impact on tHcy concentrations, highlighting the potential for targeted nutritional interventions to manage cardiovascular risks associated with H-Hcy. This trial was registered at clinicaltrials.gov as ChiCTR2100051983.
在中国，与大多数西方人群不同，MTHFR 677T等位基因是一种与多种疾病相关的罕见基因变异。导致这种遗传风险的营养和遗传因素尚不清楚。
本研究旨在阐明中国高血压人群中总同型半胱氨酸（tHcy）途径基因的遗传变异、血清tHcy浓度和营养因素之间的相互作用。
本研究分析了纳入中国精准营养与健康KAP真实世界研究（CPNAS）的1304名年龄≥18岁的中国成年高血压患者。采用磁微粒化学发光法测定血清维生素B12和叶酸浓度，使用同型半胱氨酸检测试剂盒测定tHcy浓度。通过飞行时间核酸光谱法鉴定MTHFR C677T、MTHFR A1298C和MTRR A66G多态性。
我们的研究结果显示tHcy浓度存在显著的性别差异，男性的tHcy浓度高于女性（13.95μmol/L对11.15μmol/L，P<0.001）。维生素B12和叶酸均缺乏的个体发生高同型半胱氨酸血症（H-Hcy）的风险增加（57.4%）。相比之下，单独缺乏维生素B12（31.1%）或叶酸（23.2%）的个体中H-Hcy的患病率较低。MTHFR C677T和A1298C多态性与血清tHcy浓度升高之间存在显著关联，尤其是T等位基因纯合子个体。相反，MTRR A66G基因型与tHcy浓度无显著相关性。最佳维生素B12浓度显著调节了基因型对tHcy浓度的影响，即使在高危基因型（TT）中，维生素B12和叶酸充足的个体tHcy浓度也较低。
充足的叶酸和维生素B12浓度可显著降低血清tHcy浓度，并减轻基因型对tHcy浓度的影响，突出了针对性营养干预在管理与H-Hcy相关的心血管风险方面具有的潜力。本试验在clinicaltrials.gov上注册，注册号为ChiCTR2100051983。
