Northern Ireland Centre for Food and Health, Biomedical Sciences Research Institute, Ulster University, Cromore Rd, Coleraine, BT52 1SA Northern Ireland, UK.
Northern Ireland Centre for Food and Health, Biomedical Sciences Research Institute, Ulster University, Cromore Rd, Coleraine, BT52 1SA Northern Ireland, UK.
Mol Aspects Med. 2017 Feb;53:2-9. doi: 10.1016/j.mam.2016.10.002. Epub 2016 Oct 6.
Hypertension is the leading risk factor contributing to mortality worldwide, primarily from cardiovascular disease (CVD), while effective treatment of hypertension is proven to reduce CVD events. Along with the well recognized nutrition and lifestyle determinants, genetic factors are implicated in the development and progression of hypertension. In recent years genome-wide association studies have identified a region near the gene encoding the folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) among eight loci associated with blood pressure. Epidemiological studies, which provide a separate line of evidence to link this gene with blood pressure, show that the 677C→T polymorphism in MTHFR increases the risk of hypertension by 24-87% and CVD by up to 40%, albeit with a large geographical variation in the extent of excess disease risk suggestive of a gene-environment interaction. Emerging evidence indicates that the relevant environmental factor may be riboflavin, the MTHFR co-factor, via a novel and genotype-specific effect on blood pressure. Randomized trials conducted in hypertensive patients (with and without overt CVD) pre-screened for this polymorphism show that targeted riboflavin supplementation in homozygous individuals (MTHFR 677TT genotype) lowers systolic blood pressure by 6 to 13 mmHg, independently of the effect of antihypertensive drugs. The latest evidence, that the blood pressure phenotype associated with this polymorphism is modifiable by riboflavin, has important clinical and public health implications. For hypertensive patients, riboflavin supplementation can offer a non-drug treatment to effectively lower blood pressure in those identified with the MTHFR 677TT genotype. For sub-populations worldwide with this genotype, better riboflavin status may prevent or delay the development of high blood pressure. Thus riboflavin, targeted at those homozygous for a common polymorphism in MTHFR, may offer a personalized treatment or preventative strategy for hypertension. Further investigations of this novel gene-nutrient interaction in relation to blood pressure, hypertension and hypertension in pregnancy are required.
高血压是全球导致死亡的主要危险因素，主要与心血管疾病（CVD）有关，而有效的高血压治疗已被证明可降低 CVD 事件的发生。除了公认的营养和生活方式决定因素外，遗传因素也与高血压的发生和发展有关。近年来，全基因组关联研究已在与血压相关的 8 个基因座中确定了一个位于编码叶酸代谢酶亚甲基四氢叶酸还原酶（MTHFR）的基因附近的区域。流行病学研究为将该基因与血压联系起来提供了另一条证据线，表明 MTHFR 中的 677C→T 多态性使高血压的风险增加 24-87%，CVD 的风险增加高达 40%，尽管在疾病风险过高的程度上存在较大的地理差异，提示存在基因-环境相互作用。新出现的证据表明，相关的环境因素可能是核黄素，即 MTHFR 的辅助因子，通过对血压产生一种新的、特定于基因型的影响。在经过这种多态性预筛选的高血压患者（有或无明显 CVD）中进行的随机试验表明，针对纯合子（MTHFR 677TT 基因型）的靶向核黄素补充可使收缩压降低 6-13mmHg，这独立于降压药物的作用。最新的证据表明，与这种多态性相关的血压表型可通过核黄素进行修饰，这具有重要的临床和公共卫生意义。对于高血压患者，核黄素补充可以为那些具有 MTHFR 677TT 基因型的患者提供一种非药物治疗方法，有效地降低血压。对于全世界具有这种基因型的亚人群，改善核黄素状态可能会预防或延迟高血压的发展。因此，针对 MTHFR 中常见多态性的纯合子人群的核黄素靶向治疗可能为高血压提供一种个性化的治疗或预防策略。需要进一步研究这种新型基因-营养相互作用与血压、高血压和妊娠高血压的关系。
