Proinflammatory cytokine gene polymorphisms and susceptibility to Paget's disease of bone: an association study

Background: Recent studies suggested that proinflammatory cytokines are involved in the pathophysiology of Paget's disease of bone (PDB). The purpose of this study was to evaluate whether functionally active polymorphisms of the interleukin-1α (IL-1α), interleukin-1β (IL-β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) genes would modify the occurrence and the clinical features of PDB.

Methods: Genomic DNA was extracted from 144 PDB patients and 115 healthy controls. All subjects were genotyped for the following functionally active polymorphisms in the proinflammatory cytokine genes: IL-1α-889 C>T, IL-1β-511 C>T, IL-6-174 G>C, and TNF-α-308 G>A. Allele and genotype frequencies were compared between cases and controls. The clinical characteristics of the disease were compared according to the different genotypes.

Results: Allele and genotype frequencies of the examined polymorphism resulted nearly identical in cases and controls. Examining the association with the clinical features, PDB patients carrying the C/C genotype of the IL-6 gene showed a significantly (p<0.001) higher frequency of hearing loss and primary hyperparathyroidism. No significant difference in the remaining clinical features was found. In conclusion, this study do not support the hypothesis that the examined proinflammatory genes are major genetic risk factor for PDB. However, our data suggests a role for the IL-6 gene in modifying the clinical features of the disease.