Imperial College London
Alternate

Dr Antonio J Berlanga-Taylor

Faculty of Medicine, School of Public Health

Honorary Senior Research Fellow
 
 
 
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a.berlanga

 
 
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Location

 

47 Praed StreetSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Berlanga-Taylor:2018:10.1016/j.ebiom.2018.04.010,
author = {Berlanga-Taylor, AJ and Plant, K and Dahl, A and Lau, E and Hill, M and Sims, D and Heger, A and Emberson, J and Armitage, J and Clarke, R and Knight, JC},
doi = {10.1016/j.ebiom.2018.04.010},
journal = {EBioMedicine},
pages = {133--142},
title = {Genomic response to vitamin D supplementation in the setting of a randomized, placebo-controlled trial},
url = {http://dx.doi.org/10.1016/j.ebiom.2018.04.010},
volume = {31},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Vitamin D deficiency has been associated with multiple diseases, but the causal relevance and underlying processes are not fully understood. Elucidating the mechanisms of action of drug treatments in humans is challenging, but application of functional genomic approaches in randomized trials may afford an opportunity to systematically assess molecular responses. METHODS: In the Biochemical Efficacy and Safety Trial of Vitamin D (BEST-D), a double-blind, placebo-controlled, dose-finding, randomized clinical trial, 305 community-dwelling individuals aged over 65years were randomly allocated to treatment with vitamin D3 4000IU, 2000IU or placebo daily for 12months. Genome-wide genotypes at baseline, and transcriptome and plasma levels of cytokines (IFN-γ, IL-10, IL-8, IL-6 and TNF-α) at baseline and after 12months, were measured. The trial had >90% power to detect 1.2-fold changes in gene expression. FINDINGS: Allocation to vitamin D for 12-months was associated with 2-fold higher plasma levels of 25-hydroxy-vitamin D (25[OH]D, 4000IU regimen), but had no significant effect on whole-blood gene expression (FDR<5%) or on plasma levels of cytokines compared with placebo. In pre-specified analysis, rs7041 (intron variant, GC) had a significant effect on circulating levels of 25(OH)D in the low dose, but not in the placebo or high dose vitamin D regimen. A gene expression quantitative trait locus analysis (eQTL) demonstrated evidence of 31,568 cis-eQTLs (unique SNP-probe pairs) among individuals at baseline and 34,254 after supplementation for 12months (any dose). No significant associations involving vitamin D supplementation response eQTLs were found. INTERPRETATION: We performed a comprehensive functional genomics and molecular analysis of vitamin D supplementation in a randomized, placebo-controlled trial. Although this study was limited to mostly Caucasian individuals aged over 65years, the results differ from many previous studi
AU  - Berlanga-Taylor,AJ
AU  - Plant,K
AU  - Dahl,A
AU  - Lau,E
AU  - Hill,M
AU  - Sims,D
AU  - Heger,A
AU  - Emberson,J
AU  - Armitage,J
AU  - Clarke,R
AU  - Knight,JC
DO  - 10.1016/j.ebiom.2018.04.010
EP  - 142
PY  - 2018///
SN  - 2352-3964
SP  - 133
TI  - Genomic response to vitamin D supplementation in the setting of a randomized, placebo-controlled trial
T2  - EBioMedicine
UR  - http://dx.doi.org/10.1016/j.ebiom.2018.04.010
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29685792
UR  - http://hdl.handle.net/10044/1/59318
VL  - 31
ER  -
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