Assessment of the contribution of VDR and VDBP/GC genes in the pathogenesis of celiac disease

Vitamin-D deficiency (VDD) is a global health concern. It is known to play a critical role in the immunomodulation, and thus, its metabolism could be investigated to unravel its contribution in common immune-mediated diseases, e.g., celiac disease (CD). Genotyping of SNPs from vitamin D receptor (VDR) gene, such as rs11568820 (Cdx2) and rs2228570 (Fok1) using allele specific multiplex polymerase chain reaction (ASM-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively; and rs7041 and rs4588 of vitamin D binding protein (VDBP/GC) using PCR-RFLP were done in 969 subjects including CD cases (n=506) and controls (n=463). Genotype data for 86 CD and 712 controls for rs11568820 and rs7041 were retrieved from already published Immunochip genotype data. Serum concentration of vitamin-D and vitamin D binding protein (VDBP) were measured for 283 participants (98 CD and 185 controls). rs4588-A allele was identified as protective allele [OR=0.6(0.4–0.7), P<0.0001]. Significantly reduced serum level of vitamin-D was observed in CD patients [median=16.25 ng/mL, IQR (8.94–23.60)] than in controls [median=19.94 ng/mL, IQR (13.91–28.46)] with P=0.001. Notably, rs7041-GG, rs4588-CC, and 1F (GC) haplotype of VDBP/GC showed significant association (P<0.05) with reduced serum vitamin D level. We did not find any significant association with VDBP serum concentration. Significant vitamin D and VDBP level correlations were observed in controls (spearman r = 0.3, P=0.005). The present study highlights the significance of reduced vitamin-D serum level in CD. 1F variant of VDBP and lower vitamin-D levels contribute to CD. No correlation between vitamin-D and VDBP levels suggests that vitamin-D supplementation may improve vitamin-D levels but might not affect VDBP levels in CD subjects.