Improved prediction of knee osteoarthritis progression by genetic polymorphisms: the Arthrotest Study
Por:
Blanco, FJ, Moller, I, Romera, M, Rozadilla, A, Sanchez-Lazaro, JA, Rodriguez, A, Galvez, J, Fores, J, Monfort, J, Ojeda, S, Moragues, C, Caracuel, MA, Clavaguera, T, Valdes, C, Soler, JM, Orellana, C, Belmonte, MA, Martin, F, Gimenez, S, Ucar, E, Pous, J, Bartolome, N, Artieda, M, Szczypiorska, M, Tejedor, D, Martinez, A, Montell, E, Martinez, H, Herrero, M, Verges, J
Publicada:
1 jul 2015
Resumen:
Objective. The aim of this study was to develop a genetic prognostic tool to predict radiographic progression towards severe disease in primary knee OA (KOA) patients.
Methods. This investigation was a cross-sectional, retrospective, multicentric association study in 595 Spanish KOA patients. Caucasian patients aged >= 40 years at the time of diagnosis of primary KOA of Kellgren-Lawrence grade 2 or 3 were included. Patients who progressed to Kellgren-Lawrence score 4 or who were referred for total knee replacement within 8 years after diagnosis were classified as progressors to severe disease. Clinical variables of the initial stages of the disease (gender, BMI, age at diagnosis, OA in the contralateral knee, and OA in other joints) were registered as potential predictors. Single nucleotide polymorphisms and clinical variables with an association of P < 0.05 were included in the multivariate analysis using forward logistic regression.
Results. A total of 23 single nucleotide polymorphisms and the time of primary KOA diagnosis were significantly associated with KOA severe progression in the exploratory cohort (n = 220; P < 0.05). The predictive accuracy of the clinical variables was limited: area under the curve (AUC) = 0.66. When genetic variables were added to the clinical model (full model), the prediction of KOA progression was significantly improved (AUC = 0.82). Combining only genetic variables (rs2073508, rs10845493, rs2206593, rs10519263, rs874692, rs7342880, rs780094 and rs12009), a predictive model with good accuracy was also obtained (AUC = 0.78). The predictive ability for KOA progression of the full model was confirmed on the replication cohort (two-sample Z-test; n = 62; P = 0.190).
Conclusion. An accurate prognostic tool to predict primary KOA progression has been developed based on genetic and clinical information from OA patients.
Filiaciones:
Blanco, FJ:
UDC, Serv Reumatol, INIBIC, CHUAC, La Coruna, Spain
Moller, I:
Inst Poal Reumatol, Reumatol, Barcelona, Spain
Romera, M:
Hosp Univ Bellvitge, Serv Reumatol, Lhospitalet De Llobregat, Spain
Rozadilla, A:
Hosp Univ Bellvitge, Serv Reumatol, Lhospitalet De Llobregat, Spain
Sanchez-Lazaro, JA:
Hosp Leon, Serv Traumatol, Leon, Spain
Rodriguez, A:
Hosp Santa Creu & Sant Pau, Serv Reumatol, Barcelona, Spain
Galvez, J:
Hosp Jose Maria Morales Meseguer, Serv Reumatol, Murcia, Spain
Fores, J:
Hosp Clin Barcelona, Serv Traumatol, Barcelona, Spain
Monfort, J:
Parc Salut Mar, Serv Reumatol, Barcelona, Spain
Ojeda, S:
Hosp Univ Gran Canaria Doctor Negrin, Serv Reumatol, Las Palmas Gran Canaria, Spain
Moragues, C:
Hosp Plato, Serv Reumatol, Barcelona, Spain
Caracuel, MA:
Hosp Reina Sofia, Serv Reumatol, Cordoba, Spain
Hosp Gen Castellon, Serv Reumatol, Castellon de La Plana, Spain
Clavaguera, T:
Hosp Palamos, Serv Reumatol, Palamos, Spain
Valdes, C:
Ctr Salud Atenc Primaria Fuencarral, Madrid, Spain
Soler, JM:
Hosp Badalona Germans Trias & Pujol, Serv Traumatol, Badalona, Spain
Orellana, C:
Corp Sanitaria Parc Tauli, Serv Reumatol, Sabadell, Spain
Belmonte, MA:
Hosp Gen Castellon, Serv Reumatol, Castellon de La Plana, Spain
Martin, F:
Ctr Salud Atenc Primaria Soto del Real, Madrid, Spain
Gimenez, S:
Ctr Salud Atenc Primaria Limonar, Malaga, Spain
Ucar, E:
Hosp Basurto, Serv Reumatol, Bilbao, Spain
Pous, J:
Ctr Med Teknon, Serv Traumatol, Barcelona, Spain
Bartolome, N:
Progen Biopharma SA, Dept Res & Dev, Barcelona, Spain
Artieda, M:
Progen Biopharma SA, Dept Res & Dev, Barcelona, Spain
Szczypiorska, M:
Progen Biopharma SA, Dept Res & Dev, Barcelona, Spain
Tejedor, D:
Progen Biopharma SA, Dept Res & Dev, Barcelona, Spain
Martinez, A:
Progen Biopharma SA, Dept Res & Dev, Barcelona, Spain
Montell, E:
Bioiberica SA, Pharmasci Div, Res & Dev Area, Barcelona, Spain
Martinez, H:
Bioiberica SA, Pharmasci Div, Res & Dev Area, Barcelona, Spain
Herrero, M:
Bioiberica SA, Pharmasci Div, Res & Dev Area, Barcelona, Spain
Verges, J:
Bioiberica SA, Pharmasci Div, Res & Dev Area, Barcelona, Spain
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