Serum levels of miR-199a-5p correlates with blood pressure in premature cardiovascular disease patients homozygous for the MTHFR 677C?>?T polymorphism

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.