Genomic Medicine Research Group, Biomedical Sciences Research Institute, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK.
Nutrition Innovation Centre for Food and Health (NICHE), Biomedical Sciences Research Institute, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK.
Genomics. 2020 Jan;112(1):669-676. doi: 10.1016/j.ygeno.2019.04.019. Epub 2019 Apr 25.
This investigation profiled circulating serum concentrations of microRNAs (miRNAs) in premature cardiovascular disease (CVD) patients screened for the 677C > T polymorphism in methylenetetrahydrofolate reductase (MTHFR), a risk factor for hypertension. Serum samples from 75 premature CVD patients of known MTHFR genotype were analysed for CVD-related miRNA expression, to identify those that were associated with blood pressure. Samples were collected at baseline and following intervention with riboflavin as part of a randomized controlled trial. In patients with the MTHFR 677TT genotype, expression of miR-199a-5p in serum was inversely correlated with hypertension at baseline, and with change in blood pressure in TT genotype patients who responded to riboflavin intervention. These correlations were not observed in MTHFR 677CC genotype patients. In vitro experiments and in silico data analysis provided evidence that miR-199a-5p targets SMAD4. This is the first study to link miR-199a-5p expression with hypertension in a genetically at-risk cohort of premature CVD patients.
本研究调查了在亚甲基四氢叶酸还原酶（MTHFR）677C>T 多态性筛查的早产儿心血管疾病（CVD）患者中循环血清 miRNA（miRNA）浓度，该基因是高血压的危险因素。对已知 MTHFR 基因型的 75 名早产儿 CVD 患者的血清进行了与 CVD 相关的 miRNA 表达分析，以确定与血压相关的 miRNA。这些样本是在基线时采集的，随后作为一项随机对照试验的一部分，用核黄素进行干预。在 MTHFR 677TT 基因型患者中，血清 miR-199a-5p 的表达与基线时的高血压呈负相关，与对核黄素干预有反应的 TT 基因型患者的血压变化呈负相关。在 MTHFR 677CC 基因型患者中未观察到这些相关性。体外实验和计算机数据分析提供了证据，表明 miR-199a-5p 靶向 SMAD4。这是第一项在有遗传风险的早产儿 CVD 患者队列中，将 miR-199a-5p 表达与高血压联系起来的研究。
