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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.

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