Abstract
BackgroundVitamin D deficiency or insufficiency, has been associated with atopy and lack of asthma control. Our objective was to investigate associations between variants in genes of vitamin D pathway with serum levels of 25-hydroxyvitamin D (25(OH)D), atopy, asthma and asthma severity in teenagers from Northeast Brazil.MethodsThis is a cross sectional study nested in a cohort population of asthma. 25(OH)D was quantified from 968 of 11–17 years old individuals by ELISA. Asthma diagnosis was obtained by using the ISAAC Phase III questionnaire. Specific IgE was determined by ImmunoCAP; genotyping was performed using the 2.5 HumanOmni Biochip from Illumina. Statistical analyses were performed in PLINK 1.07 and SPSS 22.1.ResultsAfter quality control, 104 Single Nucleotides Variants (SNVs) in vitamin D pathway genes, typed in 792 individuals, were included in the analysis. The allele A of rs10875694 on VDR was positively associated with atopy (OR = 1.35; 95% CI 1.01–1.81). The allele C of rs9279 on VDR, was negatively associated with asthma risk (OR = 0.66; 95% CI 0.45–0.97), vitamin D insufficiency (OR = 0.78; 95% CI 0.70–0.96) and higher VDR expression. Two variants in VDR were associated with asthma severity, the allele A of rs2189480 (OR = 0.34; 95% CI 0.13–0.89) and the allele G of rs4328262 (OR = 3.18; 95% CI 1.09–9.28). The combination of variants in CYP2R1 and CYP24A1 (GAC, to rs10500804, rs12794714 and rs3886163, respectively) was negatively associated with vitamin D production (β = − 1.24; 95% CI − 2.42 to − 0.06).ConclusionsGenetic variants in the vitamin D pathway affect vitamin D serum levels and, thus, atopy and asthma.
Highlights
Vitamin D deficiency or insufficiency, has been associated with atopy and lack of asthma control
Galvão et al Allergy Asthma Clin Immunol (2020) 16:62 (Th2) response that covers the production of cytokines such as, interleukin (IL)-4, IL-5 and IL-13 which all together orchestrate the migration of eosinophils, mast cells activation and Immunoglobulin E (IgE) production [5, 6]
Previous studies from our group in the same population of the current study have shown that 24,5% of asthma cases were attributed to atopy [10] and that IFN-γ could be an important biomarker of non-atopic asthma in this population [11]
Summary
Vitamin D deficiency or insufficiency, has been associated with atopy and lack of asthma control. Asthma affects more than 339 million people worldwide and it is estimated leading to the death of almost 400,000 people by year [1, 2]. All the other asthma phenotypes that do not include sIgE production (specific Immunoglobulin E) are classified as non-atopic [3]. The main risk factors for this asthma phenotype include poverty and dirt conditions [12]. These findings suggest that asthma in Latin America could differ from Europe and other developed countries [13]
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