Poor or no response to vitamin D was associated with poor genes (cystic fibrosis, 4 genes) Sept 2022

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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.

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In VitaminDWiki, 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
• Reasons for low response to vitamin D
• 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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VitaminDWiki - Vitamin D Binding Protein category has177 items

Vitamin D Binding Protein (GC) gene can decrease the bio-available Vitamin D that can get to cells,

• GC is not the only such gene - there are 3 others, all invisible to standard Vitamin D tests
• The bio-available calculation does not notice the effect of GC, CYP27B1, CYP24A1, and VDR
• The actual D getting to the cells is a function of measured D and all 4 genes
• There is >2X increase in 8+ health problems if have poor VDBP (GC)
• It appears that VDBP only blocks oral vitamin D,
  • but NOT Vitamin D from sun, UV, topical or inhaled (tissue activated)
  • A clue: - Vitamin D from UV is 2X better for MS than oral Vitamin D

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VitaminDWiki - Vitamin D Binding Protein list of health problems

Increased Risk	Health Problem
11 X	Preeclampsia
6.5X	T1D in SA Blacks
6 X	Food Allergy
5 X	PTSD
4 X, 5X	Kidney Cancer
4 X	Poor Response to Oral Vitamin D
3 X	Ear infection
2.8 X	MS
2 X	Colorectal Cancer
2 X	Prostate Cancer -in those with dark skins
1.3 X	Infertility

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VitaminDWiki - 3 studies in both categories Cystic Fibrosis and Magnesium

This list is automatically updated