In brief, cases were selected if they had clinically significant symptomatic OA of the hip or knee, sufficient to warrant hospital referral. They were recruited if they had either undergone joint replacement, were on the orthopaedic waiting list or Tanespimycin had been referred with symptomatic knee OA to the Nottingham knee Inhibitors,Modulators,Libraries OA clinic. Controls were recruited from hospital intravenous urogra phy waiting lists and frequency matched to cases by age and gender. Controls with no evidence of hip OA on review of their IVU radiographs were invited to take part in the study. Inhibitors,Modulators,Libraries Only individuals that met the study inclusion criteria were sampled. The parti cipation rate of eligible cases and controls was 62% and 56%, respectively. This included 1,042 knee OA cases, 1,006 hip OA cases and 1,123 non OA controls.

Data collection The GOAL study collected data using an interview admi nistered questionnaire and clinical examination. The ques tionnaire collected information Inhibitors,Modulators,Libraries on socio demographic factors, employment history, occupational Inhibitors,Modulators,Libraries activity, and sig nificant injury, and also contained detailed questions on other risk factors for OA. Weight and height were measured by a trained research nurse during the clinical examination. New knee, hand and pelvis radio graphs were taken at the clinical examination unless the participant had undergone radiography not more than two years prior to the study or had undergone total joint repla cement. Radiographic assessment and grading for features of OA have been described in detail elsewhere. Genotyping Genomic DNA was extracted from whole blood using Gentra PureGene kit.

TaqMan allelic discri mination genotyping method was applied to detect gen otype polymorphisms at the TGFb1 locus as described Inhibitors,Modulators,Libraries previously. Exposure variables Body mass index was calculated in kgm2. Possible confounding factors included age, sex, bone mineral density, nodal OA, significant joint injury and occupational risk factors. Calcaneal bone density in gcm2 was measured using DXA and the age adjusted z score was used for BMD in the analysis. The presence of interphalangeal nodes was determined during the clinical examination and nodal OA was defined as Heberdens andor Bou chards nodes present in at least two x rays of each hand. Participants self reported previous significant joint injury to the knee and hip joint.

Also included in the interviewer administered questionnaire were detailed questions about jobs held since leaving school. For each job reported, information was sought on tasks per formed on an average working day that involved 12 spe cified occupational activities such as kneeling and squatting as well as the weekly frequency of lifting dif ferent kinase inhibitor Vandetanib levels of weights. For this analysis, the longest held occupation was used. We truncated occupational exposure for patients who had undergone TJR so that the longest held job prior to TJR was selected.