Vitamin D receptor polymorphisms are associated with severity of wheezing illnesses and asthma exacerbations in children
Journal of Steroid Biochemistry and Molecular Biology April 2020, https://doi.org/10.1016/j.jsbmb.2020.105692
Katharine Leitera, Kimberley Franksa,b, Meredith L Borlanda,c, Laura Colemana,b, Leesa Harrisa,b, Peter N. Le Souefa,b, Ingrid A. Lainga,b,*
Overview Asthma and Vitamin D contains
- VitaminDWiki pages containing ASTHMA in title (164 as of Nov 2024)
- Asthma attacks reduced in half if Vitamin D level higher than 42 nanograms – RCT May 2014
- Started with 100,000 IU loading dose and has standard-of-care Asthma drug
- Asthma may be treated by Vitamin D if more than 40 ng for 12 months – Sept 2018
- Those with Asthma or COPD had half the response to Vitamin D – March 2020
- Those with Asthma need larger doses to get the same response.
- Probably need gut-friendly Vitamin D
- CDC funded study: 1.3 X Asthma risk if vaccination contained aluminum – Sept 2022
- Asthma occurrence rate reduced 3X by Vitamin D – 8 study meta-analysis - Aug 2021
- Asthma in child 2.3 X more likely if both parents asthmatic (unless add Vitamin D) – VDAART Nov 2018
- Adult-onset asthma 2X more likely if low vitamin D and not hyperallergenic – May 2018
- Children had poor lung function if mothers had low vitamin D while pregnant – Nov 2022
- 26 health factors increase the risk of COVID-19 – all are proxies for low vitamin D
- CDC list of high-risk for COVID-19 includes Asthma
- Child Asthma increased 2.1 X by antibiotics, Child milk allergy increased 4.4 X by PPI – April 2018
- Asthmatic children taking Corticosteroids had 2X more vitamin D intake, but lower levels – July 2017
- Traffic pollution increases asthma unless supplement with Vitamin D (mice) June 2018
- Childhood asthma problems eliminated for months by 600,000 IU of Vitamin D injection – June 2017
- Proof that Vitamin D Works 92 health problems prevented/treated as of Nov 2020
- Asthma has been proven to be treated by Vitamin D in at least 4 random controlled trials
- Childhood asthma still reduced 4 months after 800 IU of Vitamin D daily - RCT Feb 2016
- Respiratory Disease exacerbations (Asthma, CF, COPD) may be treated by Vitamin D – July 2019
- Women with asthma 35X more likely to be vitamin D deficient – Oct 2013
- If high vitamin D during pregnancy the child is 5X less likely to get asthma
- Asthma is treated by Vitamin D – now they are trying to understand why – Feb 2015
- Increase in vitamin D deficiency may partially explain increases in asthma and allergies – Jan 2015
- Why deficiencies in vitamin D and magnesium are linked to asthma Magnesium allows muscles to relax
- Babies 3.6X more likely to go to hospital for asthma if asthmatic mother had low vitamin D while pregnant – June 2019
- The worse the bronchial asthma, the lower the vitamin D – Jan 2017 has the following chart
click on the chart to see the study
Items in both categories Breathing and Vitamin D Receptor are listed here:
- Asthma by age 7 if wheezing before preschools and poor vitamin D Receptor - May 2023
- 2X increase risk of Asthma if a particular Vitamin D Receptor mutation – meta-analysis Feb 2022
- Atopies (allergy, asthma, rhinitis, etc.) variously associated with low Vitamin D and poor Vitamin D Receptor – Aug 2021
- Mucosal membranes (mouth, lungs, nose, intestines, etc) can activate Vitamin D – July 2020
- Respiratory problems in Children 1.4X more likely if poor Vitamin D receptor – April 2020
- Poor response to Asthma inhaler if poor Vitamin D Receptor – Dec 2019
- Microbiomes of both gut and airway are affected by Vitamin D and Vitamin D Receptor – Nov 2018
- Asthma 3.7X higher risk of poor Vitamin D Receptor (teens in Taiwan in this case) – Nov 2019
- Asthma is 20 percent more likely with a poor Vitamin D Receptor gene – meta-analysis Oct 2019
- Asthmatic children 5X more likely to have a poor Vitamin D Receptor – June 2019
- Best supplements for hay fever (Quercetin, which activates the Vitamin D receptor) - June 2019
- Upper respiratory infection associated with poor Vitamin D Receptor – Oct 2018
- Respiratory Distress Syndrome in preemies 5 X more likely if poor vitamin D receptor – Feb 2019
- Gut and airway bionome are affected by Vitamin D and Vitamin D Receptor – Nov 2018
- Pneumonia in Egyptian Children 3.6 X more likely if poor Vitamin D Receptor – Aug 2018
- Respiratory Tract Infections in children 7.4 X more likely if poor Vitamin D Receptor – 2008
- Inflammation and immune responses to Vitamin D (perhaps need to measure active vitamin D) – July 2017
- Vitamin D Receptor problems occur 5 times for often with Nasal polyposis – Nov 2016
- Vitamin D effects on lung immunity and respiratory diseases – 2011
- Childhood asthma about 1.3 times more likely if poor Vitamin D Receptor – meta-analysis Aug 2016
- Severe Pertussis is 1.5 times more likely if poor vitamin D receptor – Feb 2016
- 2X higher risk of wheezing and asthma if modified receptor genes, even if vitamin D levels OK – Sept 2015
- 2.8X higher risk of osteoporosis if COPD and modified vitamin D receptor genes – Sept 2015
- Strong Vitamin D deficiency associations in Asthma patients – Nov 2014
- Epigenetics and Vitamin D – many studies
Vitamin D Receptor is associated in over 58 autoimmune studies
The risk of 44 diseases at least double with poor Vitamin D Receptor as of Oct 2019
Vitamin D Receptor activation can be increased by any of: Resveratrol, Omega-3, Magnesium, Zinc, Quercetin, non-daily Vit D, Curcumin, intense exercise, Ginger, Essential oils, etc Note: The founder of VitaminDWiki uses 10 of the 12 known VDR activators
 Download the PDF from sci-hub via VitaminDWiki
Wheezing and asthma exacerbations are a leading cause of hospitalisations for children in developed countries [1]. Asthma is a multifactorial disease caused by a complex interaction of genetic predisposition and environmental exposures. A significant proportion of the inter-individual risk for developing asthma is due to genetic differences [2-4]. Numerous studies have identified loci, candidate genes, and single nucleotide polymorphisms (SNPs) which show linkage and association with asthma development [5-8]. However, limited studies have evaluated the association between these isolated genetic variations and mechanisms of acute wheeze and asthma.
There has been increasing interest in the role of vitamin D in wheezing and asthma. Vitamin D, a fat-soluble nutrient widely recognised for its role in bone health, also plays a role in immune regulation [9]. Its biological effects, including regulation of helper T-cell development and subsequent cytokine secretion profiles, are achieved through the regulation of gene expression, which is mediated by the vitamin D receptor (VDR) [8]. The VDR gene is located on chromosome 12, region q13-23: a region commonly linked to asthma in genomewide linkage analyses [10].
Family-based cohort studies have identified VDR genetic variants that are strongly associated with asthma traits in particular populations [7,8]. Such findings suggest that the VDR locus harbours variants that Single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene have shown linkage and association with asthma development in multiple cohort studies. However, the majority of investigations have focused on asthma phenotypes in cohorts with stable disease. We investigated the relationship between VDR SNPs and the frequency and severity of acute episodes of wheeze/asthma in a cohort of Australian children, as the ability to identify children at risk of more severe exacerbations could lead to personalized and improved genotype-specific treatment pathways. We successfully genotyped five SNPs of the VDR gene (rs2525046, rs9729, rs1544410 (BsmI), rs22239179, and rs2228570 (FokI)) in 657 children presenting to a tertiary children's hospital with acute asthma, bronchiolitis, or a wheezing illness. The relationships between VDR SNPs and exacerbation severity scores, 2-agonist use, and frequency of respiratory exacerbations were analysed using multiple regression. The rs2525046 (FokI) CT genotype was associated with higher VDR mRNA intensity levels (p = 0.007) compared to the CC genotype. A trend towards significance (p = 0.056) was identified between the rs2525046 TT genotype and higher VDR mRNA intensity levels compared to the CC genotype. Children with rs2228570 AA genotype had higher exacerbation severity scores (p = 0.001) and poorer 2-agonist treatment response (doses at 6h:p = 0.009 and 12h:p = 0.033) compared to those with the GG genotype. Children with rs1544410 (BsmI) TT genotype had lower exacerbation severity scores (p = 0.005) compared to those with the CC genotype. Children with rs2228570 GA genotype presented to and/or were admitted to hospital more times since birth with respiratory (p = 0.011) and wheezing (p = 0.021) illnesses than children with the GG genotype. No associations were identified between rs9729, rs2525046 and r2239179 polymorphisms and acute wheezing/asthma variables. These findings suggest that genetic variants at the VDR locus may play a role in acute wheeze/asthma severity in children.