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


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 VitaminDWiki, but probably not considered by this study


VitaminDWiki - Vitamin D Binding Protein category has167 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,

VitaminDWiki - Vitamin D Binding Protein list of health problems

Increased
Risk
Health Problem
11 XPreeclampsia
6.5XT1D in SA Blacks
6 XFood Allergy
5 XPTSD
4 X, 5XKidney Cancer
4 XPoor Response to Oral Vitamin D
3 XEar infection
2 X MS
2 X Colorectal Cancer
2 XProstate Cancer -in those with dark skins
1.3 XInfertility

VitaminDWiki - 3 studies in both categories Cystic Fibrosis and Magnesium

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Created by admin. Last Modification: Thursday September 8, 2022 16:03:19 GMT-0000 by admin. (Version 8)