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*
Genetics category listing contains the following
see also
- Vitamin D Receptor has
530 items - Vitamin D Binding Protein = GC has
178 items - CYP27B1 has
63 items - CYP24A1 in title of 39+ items
- CYP2R1 25+ items
- Calcidiol has
48 items - Calcitriol has
62 items - Topical Vitamin D
- Nanoemulsion Vitamin D may be a substantially better form
- 1289 genes changed with higher doses of Vitamin D - RCT Dec 2019
- CYP3A4 (7 as of Dec 2022)
- Getting Vitamin D into your body
Vitamin D blood test misses a lot
- 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
especially if it is one of 51+ diseases related to Vitamin D Receptor
2) Slightly increasing Vitamin D shows benefits (even if conventional Vitamin D test shows an increase)
3) DNA and VDR tests - 100 to 200 dollars $100 to $250
4) PTH bottoms out ( shows that parathyroid cells are getting Vitamin d)
Genes are good, have enough Magnesium, etc.
5) 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&5
Vitamin D Binding Protein category listing has178 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,
- 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
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
Drug hypersensitivity is associated with Vitamin D Binding Protein, etc. – June 2019Printer Friendly Follow this page for updates3473 visitors, last modified 13 Jun, 2019, This page is in the following categories (# of items in each category) - Vitamin D Binding Protein = GC has