Poor or no response to vitamin D was associated with poor genes (cystic fibrosis, 4 genes)
Genetic factors help explain the variable responses of young children with cystic fibrosis to vitamin D supplements
Clinical Nutrition ESPEN https://doi.org/10.1016/j.clnesp.2022.07.018
JieSongdQiongshiLudeSangita G.MuraliaManavalanGajapathyfBrandon M.WilkfDonna M.BrownfElizabeth A.WortheyfPhilip M.FarrellbcFIRST Study Group
Background & aims
Children with cystic fibrosis (CF) are susceptible to fat-soluble vitamin deficiencies unless supplemented, but even large doses of vitamin D may not prevent low 25-hydroxyvitamin D (25OHD) concentrations. The explanation for these vitamin D non-responders has been elusive. We utilized data from whole genome sequencing (WGS) to test the hypothesis that genetic variations predict responsiveness to vitamin D supplementation in a prospective cohort study of children with CF in the first 3 years of life.
Methods
One hundred and one infants born during 2012–2017 and diagnosed with CF through newborn screening were studied. Serum 25OHD concentrations and vitamin D supplement doses were assessed during early infancy and annually thereafter. WGS was performed, the resultant variant calling files processed, and the summary statistics from a recent genome-wide association study were utilized to construct a polygenic risk score (PRS) for each subject.
Results
Overall, the prevalence of vitamin D insufficiency (<30 ng/mL) was 21% in the first 3 years of life. Among the 70 subjects who always adhered to vitamin D supplement doses recommended by the US CF Foundation guidelines, 89% were responders (achieved vitamin D sufficiency) by 3 years of age, while 11% were transient or non-responders. Multiple regression analysis revealed that PRS was a significant predictor of 25OHD concentrations (p < 0.001) and the likelihood of being an earlier responder in the first 3 years of life (p < 0.01). A limited SNP analysis revealed variants in four important genes (
GC (Vitamin D Binding Protein)
LIPC (Hepatic Lipase)
CYP24A1, and
PDE3B)
that were shown to be associated with 25OHD concentrations and vitamin D responder status. Other determinants included vitamin D supplement dose, season at 25OHD measurement, and pancreatic functional status.
Conclusions
Applying WGS in conjunction with utilizing a PRS approach revealed genetic variations that partially explain the unresponsiveness of some children with CF to vitamin D supplementation. Our findings suggest that a nutrigenomics strategy could help promote personalized treatment in CF.
In Vitamin D Life, but probably not considered by this study
Half of Cystic Fibrosis patients have low Magnesium levels – April 2022
Cystic Fibrosis probably treated by Vitamin D (if use enough of the right type ) – Oct 2019
Cystic fibrosis problems cut in half by Omega-3 – RCT June 2015
Vitamin D Receptor missed by most GWAS studies as it does not affect the Vitamin D in the blood, just the cells
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Vitamin D Life - Vitamin D Binding Protein list of health problems
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Vitamin D Life - studies in both categories Cystic Fibrosis and Magnesium
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