Genetic polymorphisms in vitamin D pathway influence 25(OH)D levels and are associated with atopy and asthma

Abstract

Background Vitamin 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. Methods This 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. Results After 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). Conclusions Genetic variants in the vitamin D pathway affect vitamin D serum levels and, thus, atopy and asthma.

Modern understanding of vitamin D and the genetic regulation of inflammation in various clinical models

“…В основе концепции настоящего обзора литературы положена научная гипотеза о том, что воспаление, являющееся основой различных заболеваний, имеет общие особенности, этапы, патофизиологически активные вещества, контролирующие активность воспалительных реакций, и общий генетический контроль [1][2][3]. Метаболиты витамина D (25(OH)D, 1,25(ОН)D) являясь патофизиологически активными молекулами активируют и ингибируют воспалительный процесс, в том числе, оказывая влияние на цитокины и их рецепторы (IL-1β, IL-1Ra, TNF-α, INF-γ, IL-4, IL-10) [4][5][6]. В свою очередь продукция патофизиологически активных веществ находится под контролем гена рецептора витамина D (VDR) и генов цитокинов (IL1-β/+3953, IL1RN*VNTR, TNFA*G-308A) [7][8][9].…”

Genetic Determinants of Poor Response to Treatment in Severe Asthma

“…The active metabolite of vitamin D, 1α-25-dihydroxyvitamin D, has a substantial immunomodulatory influence on the expression of proinflammatory transcriptional regulators, the inflammatory cellular response, cytokines, and IgE regulation. Variants in the vitamin D pathway gene (VDR, CYP2R1, CYP24A1, CYP27B1, DBP) are related, typically, to molecular pathways that affect the phenotype of asthma [43].…”

Vitamin D receptor gene polymorphisms in atopy

“…While other three VDR variants were associated with increased risk of vitamin D insufficiency: rs59128934(G), rs7965274(T), and rs2853564(C). 35…”

“…26 , Nasiri-Kalmarzi et al28 , Mohamed and Abdel-Rehim 31 , Galvão et al35 YesNo b Rodrigues Simões et al27 , Kilic et al32 No Yes Velankar et al38 , Kim et al39 , Dogru and Suleyman 40 ,. Wu et al41 Haridas et al43 , Su et al46 , D'Auria et al47 , Mohamed et al48 Abbreviations: SNPs, single-nucleotide polymorphisms; VDR, vitamin D receptor.…”