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Vitamin D non-responders may have one or more poor genes: GC, LIPC, CYP24A1, and PDE3B – Oct 2022

Genetic factors help explain the variable responses of young children with cystic fibrosis to vitamin D supplements

Clin Nutr ESPEN 2022 Oct;51:367-376. doi: 10.1016/j.clnesp.2022.07.018
HuiChuan J Lai 1 , Jie Song 2 , Qiongshi Lu 3 , Sangita G Murali 4 , Manavalan Gajapathy 5 , Brandon M Wilk 5 , Donna M Brown 5 , Elizabeth A Worthey 5 , Philip M Farrell 6 , FIRST 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 1% 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, LIPC, 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.

VitaminDWiki - Genetics category contains

313 articles in the Genetics category

see also

Vitamin D blood test misses a lot
Blood Test Misses a lot (VDW 3439)

  • Vitamin D from coming from tissues (vs blood) was speculated to be 50% in 2014, and by 2017 was speculated to be 90%
  • Note: Good blood test results (> 40 ng) does not mean that a good amount of Vitamin D actually gets to cells
  • A Vitamin D test in cells rather than blood was feasible (2017 personal communication)
  •    Commercially available 2019
    • However, test results would vary in each tissue due to multiple genes
  • Good clues that Vitamin D is being restricted from getting to the cells
    1) A vitamin D-related health problem runs in the family
    2) Slightly increasing Vitamin D shows benefits (even if conventional Vitamin D test shows an increase)
    3) Vitamin D Receptor test (<$30) scores are difficult to understand in 2016
    • easier to understand the VDR 23andMe test results analyzed by FoundMyFitness in 2018

    4) Back Pain

VitaminDWiki - Vitamin D Binding Protein category contains 169 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,

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