Vitamin D Receptor Genotype Modulates the Correlation between Vitamin D and Circulating Levels of let-7a/b and Vitamin D Intake in an Elderly Cohort

Background and Aims: Circulating microRNAs (miRNAs) are linked to disease and are potential biomarkers. Vitamin D may modulate miRNA profiles, and vitamin D status has been linked to risk of disease, including cardiovascular disease and cancers. We hypothesise that genotypic variance influences these relationships. We examined the correlations between vitamin D intake and circulating levels of the miRNAs let-7a/b, and the involvement of two common vitamin D receptor (VDR) polymorphisms, BsmI and ApaI. Methods: Two hundred participants completed food frequency and supplement questionnaires, and were assayed for circulating let-7b expression by qPCR. Polymorphisms were detected using restriction fragment length polymorphism-PCR. Results: let-7b expression negatively correlated with vitamin D intake (r(s) = -0.20, p = 0.005). The magnitude and direction of correlation were maintained in the presence of the BsmI restriction site (r(s) = -0.27, p = 0.0005). However, in the absence of BsmI restriction site, the direction of the correlation was reversed (r(s) = + 0.319, p = 0.0497). These correlations were significantly different (z-score = 2.64, p = 0.0085). The correlation between vitamin D intake and let-7a was only significant in those without the ApaI restriction site. Conclusions: The correlation between vitamin D intake and let-7a/b expression in this cohort varies with VDR genotype. This study highlights the importance of considering underlying genotypic variance in miRNA expression studies and in nutritional epigenetics generally. (C) 2015 S. Karger AG, Basel