VDR gene polymorphism is associated with canine atopic dermatitis and reduced cutaneous VDR expression despite normal serum vitamin D: a case-control study

Vitamin D deficiency is implicated in human atopic dermatitis, but its role in canine AD (CAD) is unclear. Vitamin D signaling requires both sufficient ligand (25(OH)D) and a functional vitamin D receptor (VDR). The main aim of this study was to investigate whether serum 25(OH)D concentrations and VDR gene polymorphism(s) are associated with CAD, and to compare cutaneous VDR/filaggrin expression and serum vitamin D levels between affected and healthy dogs. Twenty-nine client-owned dogs with CAD diagnosed using Favrot’s criteria and 21 age- and sex-matched healthy control dogs from a hospital population. Genotyping for two VDR polymorphisms (rs851938503, rs852028008) was performed using ARMS-PCR. VDR and filaggrin mRNA expression in skin biopsies was quantified by qRT-PCR. Serum 25-hydroxyvitamin D concentrations were measured by HPLC. At rs851938503, 72.4% (21/29) of CAD dogs carried ≥ 1 mutant allele vs. 33.3% (7/21) of controls. After adjusting for breed using Mantel–Haenszel analysis, the odds of CAD remained significantly increased in dogs with ≥ 1 mutant allele (pooled OR = 4.97; 95% CI: 2.63–9.40; p < 0.001). Two mutant homozygotes (6.9% of CAD) were identified, both affected. No rs852028008 mutants were detected. Cutaneous VDR mRNA was 4.1-fold lower (95% CI: 2.5–6.8) and filaggrin 6.2-fold lower (95% CI: 3.8–10.1) in CAD vs. controls. Mean serum vitamin D did not differ between CAD (36.40 ± 3.20 ng/mL) and controls (37.35 ± 2.40 ng/mL). This is the first evidence in dogs that a VDR polymorphism can be associated with CAD despite normal serum vitamin D concentrations, suggesting a dissociation between circulating ligand and receptor genotype that points toward cutaneous vitamin D signaling resistance as a potential pathomechanism in CAD, analogous to findings in human atopy.