VDR and GC gene polymorphisms modulate the risk of lumbar disc degeneration in Iran

Objective: Lumbar disc degeneration (LDD) occurs commonly in humans. Vitamin D metabolic and signaling pathway plays a significant role in intervertebral disc degeneration. The aim of this study was to evaluate the influence of the genetic polymorphism in the two key genes of 1,25-(OH)(2)-D-3 pathway, VDR (vitamin D receptor) and GC (group-specific component), in LDD development. Patients and Methods: Two single-nucleotide polymorphisms, VDR rs2228570 (FokI) and GC rs7041, were genotyped in 180 patients with LDD and 230 healthy individuals. Genomic DNA was extracted from whole peripheral blood. VDR and GC genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: A significant difference in genotype distributions of rs2228570 in VDR and rs7041 in GC gene were observed between cases and controls (P=.01 and. 005, respectively). The VDR AA homozygous genotype was seen in 30(16.7%) patients with LDD and 20(8.7%) controls (codominant model: OR = 2.48; 95% CI 1.30-4.73, P=.005) with an estimated approximately 2.5-fold risk of developing LDD in individuals with this genotype. Moreover, higher grades of disc degeneration were more related to VDR A allele. The minor allele of GC rs7041 was associated with a decreased risk of LDD (OR = 0.69; 95% CI 0.44-0.82, P=.001). Conclusion: In conclusion, our results suggest for the first time that the genetic variants of VDR and GC genes contribute to genetic predisposition to LDD in Iran. These findings need further validation in the large multicenter case-control studies.