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Drug hypersensitivity is associated with Vitamin D Binding Protein, etc. – June 2019

IDENTIFICATION OF NOVEL BIOMARKERS FOR DRUG HYPERSENSITIVITY AFTER SEQUENCING OF THE PROMOTER AREA IN 16 GENES OF THE VITAMIN D PATHWAY AND THE HIGH-AFFINITY IgE RECEPTOR

Front. Genet. | doi: 10.3389/fgene.2019.00582
Gemma Amo1, Manuel Martí2, Jasús M. García-Menaya3, Concepción Cordobés4, José Antonio Cornejo-García4, Natalia Blanca Lopez5, Inmaculada Doña6, José A. Agúndez2 and Elena García-Martín7*

VitaminDWiki

Genetics category listing contains the following

262 articles in the Genetics category

see also

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

  • Snapshot of the literature by VitaminDWiki as of early 2019
  • 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 results from a blood test (> 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
       especially if it is one of 51+ diseases related to Vitamin D Receptor
    2) Slightly increasing Vitamin D show 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
        probably want at least 2 clues before taking adding vitamin D, Omega-3, Magnesium, Resveratrol, etc
          The founder of VitaminDWiki took action with clues #3&4

Vitamin D Binding Protein category listing has 138 items and the following introduction

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,


The prevalence of allergic diseases and drug hypersensitivity reactions (DHRs) during recent years is increasing. Both, allergic diseases and DHRs seem to be related to an interplay between environmental factors and genetic susceptibility. In recent years, a large effort in the elucidation of the genetic mechanisms involved in these disorders has been made, mostly based on case-control studies, and typically focusing on isolated SNPs. These studies provide a limited amount of information, which now can be greatly expanded by the complete coverage that Next Generation Sequencing techniques offer.

In this study, we analysed the promoters of sixteen genes related to the Vitamin D pathway and the high-affinity IgE receptor, including FCER1A, MS4A2, FCER1G, VDR, GC, CYP2R1, CYP27A1, CYP27B1, CYP24A1, RXRA, RXRB, RXRG, IL4, IL4R, IL13, and IL13RA1. The study group was composed of patients with allergic rhinitis plus asthma (AR+A), patients with hypersensitivity to beta-lactams (BLs), to NSAIDs including selective hypersensitivity (SH) and cross-reactivity (CR), and healthy controls without antecedents of atopy or adverse drug reactions.

We identified 148 gene variations, 43 of which were novel. Multinomial analyses revealed that three SNPs corresponding to the genes FCER1G (rs36233990 and rs2070901), and GC (rs3733359), displayed significant associations and, therefore, were selected for a combined dataset study in a cohort of 2476 individuals. The strongest association was found with the promoter FCER1G rs36233990 SNP that alters a transcription factor binding site. This SNP was over-represented among AR+A patients and among patients with IgE-mediated diseases, as compared with control individuals or with the rest of patients in this study. Classification models based on the above-mentioned SNPs were able to predict correct clinical group allocations in patients with DHRs, and patients with IgE-mediated DHRs. Our findings reveal gene promoter SNPs that are significant predictors of drug hypersensitivity, thus reinforcing the hypothesis of a genetic predisposition for these diseases.

Keywords: next-generation sequencing (NGS), Vitamin D, high-affinity IgE receptor I (FcεRI), NSAIDs (non-steroidal anti-inflammatory drugs), beta lactam antibiotic, Drugs hypersensitivity, allergic rhinitis, Asthma


Created by admin. Last Modification: Thursday June 13, 2019 23:33:15 GMT-0000 by admin. (Version 1)
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