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 (<i>VDR</i>) polymorphisms, <i>Bsm</i>I and <i>Apa</i>I. 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 <i>Bsm</i>I restriction site (r_s = -0.27, p = 0.0005). However, in the absence of <i>Bsm</i>I 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 <i>Apa</i>I restriction site. Conclusions: The correlation between vitamin D intake and let-7a/b expression in this cohort varies with <i>VDR</i> genotype. This study highlights the importance of considering underlying genotypic variance in miRNA expression studies and in nutritional epigenetics generally.