title: 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.
abstract: OBJECTIVE
  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.affiliation: School of Environmental and Life Sciences, University of Newcastle, Ourimbah, N.S.W., Australia.
authors.forename: Emma Louise
authors.initials: EL
authors.lastname: Beckett
authors.forename: Charlotte
authors.initials: C
authors.lastname: Martin
authors.forename: Konsta
authors.initials: K
authors.lastname: Duesing
authors.forename: Patrice
authors.initials: P
authors.lastname: Jones
authors.forename: John
authors.initials: J
authors.lastname: Furst
authors.forename: Zoe
authors.initials: Z
authors.lastname: Yates
authors.forename: Martin
authors.initials: M
authors.lastname: Veysey
authors.forename: Mark
authors.initials: M
authors.lastname: Lucock
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D054647:Nutrigenomics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018167:Receptors, Calcitriol / Q000235:genetics*; D014807:Vitamin D / Q000008:administration & dosage* / Q000097:blood*
chemical_list: D035683:MicroRNAs; D018167:Receptors, Calcitriol; C579457:VDR protein, human; C487931:mirnlet7 microRNA, human; D014807:Vitamin D