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 (rs=-0.20, p=0.005). The magnitude and direction of correlation were maintained in the presence of the BsmI restriction site (rs=-0.27, p=0.0005). However, in the absence of BsmI restriction site, the direction of the correlation was reversed (rs=+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.
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 (rs=-0.20, p=0.005). The magnitude and direction of correlation were maintained in the presence of the BsmI restriction site (rs=-0.27, p=0.0005). However, in the absence of BsmI restriction site, the direction of the correlation was reversed (rs=+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.
Authors: Joëlle V Fritz; Anna Heintz-Buschart; Anubrata Ghosal; Linda Wampach; Alton Etheridge; David Galas; Paul Wilmes Journal: Annu Rev Nutr Date: 2016-05-13 Impact factor: 11.848