−511 C/T IL1B gene polymorphism is associated to resistance to bisphosphonates treatment in Paget disease of bone

Abstract

[EN]Introduction: Osteoclasts are the most important cells involved in the pathogenesis of Paget disease of bone (PDB). Cytokines stimulate osteoclast differentiation and activation, with some of them over-expressed in pagetic osteoclasts. We have assessed whether genetic variability in genes coding of proteins from the IL1 pathway clustered in chromosome 2 is associated with clinical characteristics and the therapeutic response of patients with PDB. Methods: We have studied −511 C/T and +3953 T/C polymorphisms of the IL1B gene, a HinfI polymorphism in the 5′UTR of the IL1R1 gene, and a variable number of tandem repeats (VNTR) in the intron 2 of the IL1RN gene, in 165 patients diagnosed as suffering from PDB and in 122 healthy controls. Distribution of genotypes and alleles was studied for association with clinical and laboratory data and response to bisphosphonate (BSP) treatment. Results: No differences were observed in the distribution of genotypes or alleles between PDB patients and control subjects. We also failed to detect differences concerning epidemiological, clinical and laboratory data in the series of PDB patients. However, the −511 CC genotype of the IL1B gene was associated with a higher percentage of resistance to BSP (49% vs. 20%; P = 0.00 for all BSP, 60% vs. 39%, P = 0.17 for etidronate, 50% vs. 37% P = 0.53 for clodronate, 48 vs. 34% P = 0.05 for tiludronate and 50% vs. 4% P = 0.01 for risedronate). Conclusions: Our results suggest that the −511 CC genotype of the IL1B gene could be related to resistance to bisphosphonates in patients with PDB.