Genetic variants in the optineurin gene are associated with disease severity in Paget's disease of bone

R. Obaid, W. D. Fraser, P. L. Selby, S. H. Ralston, O. M. Albagha

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Abstract / Description of output

Paget's disease of bone (PDB) is a common disease characterised by focal increases in bone remodelling leading to bone pain and other clinical complications such as bone deformity, fracture, deafness, and osteoarthritis. Mutations in SQSTM1 gene are known to cause about 10% of PDB cases and previous studies have shown that SQSTM1 mutations are associated with disease severity (Visconti et al. JBMR 2010). Recent genome wide association studies identified further susceptibility genes for PDB including CSF1, OPTN, and TNFRSF11A (Albagha et al. Nat. Genet. 2010). The risk allele “T” of the common variant rs1561570 in the OPTN gene was associated with PDB risk (P = 6.9 × 10−13; OR = 1.5). OPTN encodes optineurin, a ubiquitous cytoplasmic protein with possible role in the NFkB signalling pathway, but its role in bone metabolism is yet to be defined. In this study we investigated the relationship between rs1561570 in the OPTN gene and disease severity in 635 PDB patients without SQSTM1 mutations derived from the PRISM trial. A disease severity score was devised based on several clinical features including: number of affected bones, clinical evidence of bone deformity, the presence of bone pain, bone fractures, requirement of orthopaedic surgery, and the use of hearing aid for deafness. The association between rs1561570 and disease severity score was investigated using general linear model ANOVA adjusting for age and gender. Analysis results showed significant association between rs1561570 and severity score so that carriers of the risk allele “T” had higher severity score (6.02 ± 0.11) compared to non-carriers (5.39 ± 0.11; P = 0.031). We also found a trend for reduced quality of life (as assessed by SF36 physical summary score) in patients who carried the risk allele (36.8 ± 1.41) compared to those who did not (39.3 ± 0.5; P = 0.09). In conclusion, our results showed that OPTN gene variants are associated with disease severity and complications of PDB. These findings could be of clinical value in identifying patients (who are SQSTM1 negative) at risk of developing severe disease, however further studies in larger cohorts will be required to confirm these findings.
Original languageEnglish
Pages (from-to)S157-S157
Number of pages1
Publication statusPublished - 7 May 2011


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