The association between single nucleotide polymorphism in vitamin D receptor and calcium oxalate urolithiasis in dogs

Abstract

Background Polymorphisms of the vitamin D receptor (VDR) are associated with calcium oxalate (CaOx) nephrolithiasis in humans. Objectives To investigate the association between VDR polymorphisms and susceptibility to CaOx urolithiasis in dogs. Animals Thirty‐five dogs with CaOx urolithiasis were compared with 40 stone‐free dogs. Methods This was a case‐control study. Two VDR gene polymorphisms (rs851998024 and rs852900542) were detected by specific TaqMan real‐time polymerase chain reaction assay, and their relationship with serum 1,25‐dihydroxyvitamin D, serum and urinary electrolyte concentrations was evaluated. Results The distribution of the rs852900542 polymorphism was significantly different between the case and the control dogs (x2 = 6.369, P = .04). Dogs with a CC or CT genotype had an increased risk of CaOx stones than those with the TT genotype (odds ratio = 3.82, 95% confidence interval 1.04‐13.98). The CaOx dogs with the TT genotype had a significantly lower urinary calcium‐to‐creatinine ratio than the CT+CC genotypes. 1,25‐(OH)2D concentrations did not differ between the cases and the controls (308.7 ± 217.4 vs 286.7 ± 185.1 pg/mL, P = .45). Conclusions and Clinical Importance This finding suggests that vitamin D metabolism might play a role in CaOx stone formation in dogs.

Serum 25‐hydroxyvitamin D concentrations in dogs with coccidioidomycosis and variables associated with extent of clinically evident disease

“…19 There were two primary limitations that could have hindered identification of vitamin D differences in our study as well as 17,18,51,52 Results from two recent studies that included molecular analyses of VDR gene polymorphisms suggest that genetics could potentially influence the vitamin D metabolic pathway and have clinical value in dogs, as it does in humans. 24,53 The odds of disseminated disease were 7.5 time higher in dogs with quantitative IgG titers ≥1:32 than dogs with results below this although this result should be interpreted cautiously because of the wide confidence intervals and the classification performance of the cut-off value. While the current study is the first to report an association between increasing baseline serum IgG titers and form of coccidioidomycosis in dogs, this relationship was identified in humans more than 70 years ago.…”

“…These genetic variants have yielded several phenotypic derangements such as low circulating 25(OH)D concentrations, decreased cellular availability because of increased VDBP affinity, or lower cellular utilization because of decreased number or affinity for vitamin D receptors (VDR) 17,18,51,52 . Results from two recent studies that included molecular analyses of VDR gene polymorphisms suggest that genetics could potentially influence the vitamin D metabolic pathway and have clinical value in dogs, as it does in humans 24,53 …”

“…17 , 18 , 51 , 52 Results from two recent studies that included molecular analyses of VDR gene polymorphisms suggest that genetics could potentially influence the vitamin D metabolic pathway and have clinical value in dogs, as it does in humans. 24 , 53 …”

Characterization of the urogenital microbiome in Miniature Schnauzers with and without calcium oxalate urolithiasis

“…Calcium oxalate (CaOx) urolithiasis is increasingly common and highly recurrent in dogs 1,2 . Various genetic, metabolic, and dietary variables contribute to urolith formation, but the etiology of CaOx urolithiasis remains incompletely understood 3‐8 . Emerging interest in the role of the microbiome in CaOx urolith formation in humans has exposed new perspectives on disease pathogenesis.…”

“… 1 , 2 Various genetic, metabolic, and dietary variables contribute to urolith formation, but the etiology of CaOx urolithiasis remains incompletely understood. 3 , 4 , 5 , 6 , 7 , 8 Emerging interest in the role of the microbiome in CaOx urolith formation in humans has exposed new perspectives on disease pathogenesis. For instance, both microbiological culture and DNA sequencing methods confirm that CaOx uroliths themselves possess a unique microbiome.…”