Association of MTHFR C677T, MTHFRA1298C, and MTRRA66G Gene Polymorphisms with Hyperhomocysteinemia and Its Modulation by the Combined Effect of Vitamin B12 and Folate in Chinese Population with Hypertension

IF 3.7 3区医学 Q2 NUTRITION & DIETETICS

Journal of Nutrition Pub Date : 2025-04-01 DOI:10.1016/j.tjnut.2024.09.003

Sultan Mehmood Siddiqi , Lishun Liu , Yiming Du , Yun Song , Ping Chen , Shuqun Li , Qiangqiang He , Ziyi Zhou , Jiafeng Xu , Jie Bai , Binyan Wang , Xianhui Qin , Anam Mehmood , Liu Xiuqing , Xiaoxu Cheng , Han-Ping Shi

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Abstract

Background

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.

Objective

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.

Methods

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.

Results

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).

Conclusions

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.

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中国高血压人群中 MTHFR C677T、MTHFRA1298C 和 MTRRA66G 基因多态性与高同型半胱氨酸血症的关系，以及维生素 B12 和叶酸对其的联合调节作用。

背景：在中国，与大多数西方人群不同，MTHFR 677T 等位基因是一种与各种疾病相关的罕见遗传变异。造成这种遗传风险的营养和遗传因素仍不清楚：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 水平和营养因素之间的相互作用：本研究分析了参加中国精准营养与健康 KAP 真实世界研究（CPNAS）的 1304 名 18 岁及以上中国高血压成年人。采用磁性微粒子化学发光法测定血清中维生素 B12 和叶酸的水平，采用 Hcy 检测试剂盒测定 tHcy 的水平。通过飞行时间核光谱法对 MTHFR C677T、MTHFR A1298C 和 MTRR A66G 多态性进行了鉴定：我们的研究结果表明，tHcy水平存在明显的性别差异，男性的tHcy水平高于女性（13.95 μmol/L vs. 11.15 μmol/L，p < 0.001）。同时缺乏维生素 B12 和叶酸的人患 H-Hcy 的风险更高（57.4%）。相比之下，仅缺乏维生素 B12（31.1%）或叶酸（23.2%）者的 H-Hcy 患病率较低。研究发现，MTHFR C677T 和 A1298C 多态性与血清 tHcy 水平升高之间存在显著关联，尤其是在 T 等位基因同源的个体中。相反，MTRR A66G 基因型与 tHcy 水平没有显著相关性。最佳维生素 B12 浓度可显著调节基因型对 tHcy 水平的影响，即使在高风险基因型（TT）中，维生素 B12 和叶酸充足的个体也会表现出较低的 tHcy 水平：结论：充足的叶酸和维生素 B12 可显著降低血清中的 tHcy 浓度，并减轻基因型对 tHcy 水平的影响，这凸显了有针对性的营养干预措施在控制与高同型半胱氨酸血症相关的心血管风险方面的潜力：该试验的临床研究方案（CPNAS）已在ClinicalTrials.gov上正式注册，标识号为ChiCTR2100051983。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Nutrition 医学-营养学

CiteScore

7.60

自引率

4.80%

发文量

260

审稿时长

39 days

期刊介绍： The Journal of Nutrition (JN/J Nutr) publishes peer-reviewed original research papers covering all aspects of experimental nutrition in humans and other animal species; special articles such as reviews and biographies of prominent nutrition scientists; and issues, opinions, and commentaries on controversial issues in nutrition. Supplements are frequently published to provide extended discussion of topics of special interest.