Rheumatoid Arthritis: Naranjo A

Julià A, Ballina J, Cañete JD, Balsa A, Tornero-Molina J, Naranjo A, Alperi-López M, Erra A, Pascual-Salcedo D, Barceló P, Camps J, Marsal S. · Institut de Recerca, Hospital Universitari Vall d'Hebron, Barcelona, Spain. · Arthritis Rheum. · Pubmed #18668548 links to  free full text

Abstract: OBJECTIVE: To identify new genes associated with susceptibility to rheumatoid arthritis (RA), using a 2-stage genome-wide association study. METHODS: Following a liability-based study design, we analyzed 317,503 single-nucleotide polymorphisms (SNPs) in 400 patients with RA and 400 control subjects. We selected a group of candidate SNPs for replication in an independent group of 410 patients with RA and 394 control subjects. Using data from the 3 previous genome-wide association studies in RA, we also looked for genomic regions showing evidence of common association signals. Finally, we analyzed the presence of genome-wide epistasis using the binary test implemented in the PLINK program. RESULTS: We identified several genomic regions showing evidence of genome-wide association (P < 1 x 10(-5)). In the replication analysis, we identified KLF12 SNP rs1324913 as the most strongly associated SNP (P = 0.01). In our study, we observed that this SNP showed higher significance than PTPN22 SNP rs2476601, in both the genome-wide association studies and the replication analyses. Furthermore, the integration of our data with those from previous genome-wide association studies showed that KLF12 and PTPRT are the unique loci that are commonly associated in 3 different studies (P = 0.004 and P = 0.002 for KLF12 in the Wellcome Trust Case Control Consortium study and the Brigham and Women's Rheumatoid Arthritis Sequential Study genome-wide association study, respectively). The genome-wide epistasis analysis identified several SNP pairs close to significance after multiple test correction. CONCLUSION: The present genome-wide association study identified KLF12 as a new susceptibility gene for RA. The joint analysis of our results and those from previous genome-wide association studies showed genomic regions with a higher probability of being genuine susceptibility loci for RA.

Naranjo A, Sokka T, Descalzo MA, Calvo-Alén J, Hørslev-Petersen K, Luukkainen RK, Combe B, Burmester GR, Devlin J, Ferraccioli G, Morelli A, Hoekstra M, Majdan M, Sadkiewicz S, Belmonte M, Holmqvist AC, Choy E, Tunc R, Dimic A, Bergman M, Toloza S, Pincus T, Anonymous00244. · Hospital de Gran Canaria Dr, Negrin, University of Las Palmas de Gran Canaria, Barranco de la Ballena s/n 35011, Spain. · Arthritis Res Ther. · Pubmed #18325087 links to  free full text

Abstract: INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. RESULTS: Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries. CONCLUSION: In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.

Sokka T, Kautiainen H, Toloza S, Mäkinen H, Verstappen SM, Lund Hetland M, Naranjo A, Baecklund E, Herborn G, Rau R, Cazzato M, Gossec L, Skakic V, Gogus F, Sierakowski S, Bresnihan B, Taylor P, McClinton C, Pincus T, Anonymous00159. · Arkisto/Tutkijat, Jyvaskyla Central Hospital, 40620 Jyvaskyla, Finland. · Ann Rheum Dis. · Pubmed #17412740 No free full text.

Abstract: OBJECTIVE: To conduct a cross-sectional review of non-selected consecutive outpatients with rheumatoid arthritis (RA) as part of standard clinical care in 15 countries for an overview of the characteristics of patients with RA. METHODS: The review included current disease activity using data from clinical assessment and a patient self-report questionnaire, which was translated into each language. Data on demographic, disease and treatment-related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28-joint count) within and between countries was graphically analysed. A median regression model was applied to analyse differences in disease activity between countries. RESULTS: Between January 2005 and October 2006, the QUEST-RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) project included 4363 patients from 48 sites in 15 countries; 78% were female, >90% Caucasian, mean age was 57 years and mean disease duration was 11.5 years. More than 80% of patients had been treated with methotrexate in all but three countries. Overall, patients had an active disease with a median DAS28 of 4.0, with a significant variation between countries (p<0.001). Among 42 sites with >50 patients included, low disease activity of DAS28 <or=3.2 was found in the majority of patients in seven sites in five countries; in eight sites in five other countries, >50% of patients had high disease activity of DAS28 >5.1. CONCLUSIONS: This international multicentre cross-sectional database provides an overview of clinical status and treatments of patients with RA in standard clinical care in 2005-6 including countries that are infrequently involved in clinical research projects.

Naranjo A, Carmona L, Gavrila D, Balsa A, Belmonte MA, Tena X, Rodríguez-Lozano C, Sanmartí R, González-Alvaro I, Anonymous00225. · Rheumatology Department, Hospital Dr Negrín, Las Palmas, Spain. · Clin Exp Rheumatol. · Pubmed #15301239 No free full text.

Abstract: OBJECTIVE: To estimate the prevalence of anterior atlantoaxial subluxation (AAS) in patients with rheumatoid arthritis (RA), and to analyse its association with disease markers. METHODS: Cross-sectional analysis of a cohort of RA patients randomly selected from the clinical registries of 34 centres. AAS, defined as an atlantoaxial displacement in cervical spine X-rays greater than 3 mm on flexion films, was actively searched for. Bivariate and multivariate analysis was performed to examine its association with clinical, functional, and treatment variables. RESULTS: AAS was found in 88 out of 736 patients with available cervical radiographs, (prevalence and 95% confidence interval [CI]: 12% [9.7-14.2]). The presence of AAS was highly associated with a Larsen score (0-150) over 50 (OR and 95% CI: 5.31 [2.68-10.55]), RA duration of more than 10 years (4.48 [2.70-7.44]), disease onset before age 50 (4.15 [2.42-7.12]), eye involvement (3.93 [1.63-9.46]), and previous RA related surgery (3.90 [2.46-6.19]). No association was found with rheumatoid factor. Multivariate analysis showed that a disease onset before the age of 50, the number of previous DMARD, and, above all, a Larsen score greater than 50 were important independent factors associated with AAS. There is a 33% increased risk for AAS every 10 units up in the Larsen score. CONCLUSION: AAS is frequent in RA patients, particularly in those with markers of erosive disease.

Naranjo A, Marrero-Pulido T, Ojeda S, Francisco F, Erausquin C, Rúa-Figueroa I, Rodríguez-Lozano C, Hernández-Socorro CR. · Section of Rheumatology, Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Spain. · Scand J Rheumatol. · Pubmed #11922195 No free full text.

Abstract: OBJECTIVE: To assess the diagnostic value of ultrasonography (US) in the evaluation of arthritic shoulder joints, especially in painless shoulders. METHODS: US examinations were performed in 57 consecutive patients with rheumatoid arthritis (114 shoulders) and in 32 controls (32 shoulders), using a 7.5 MHz linear probe and a standardized study protocol. US findings were compared with clinical, laboratory, and radiological data to find any relationship. RESULTS: Abnormal sonographic findings were found in 80 shoulders (70%); the most common were lesions in the supraspinatus tendon (38%), subacromial-subdeltoid bursitis (29%), bone erosions of the humeral head (20%), glenohumeral joint ellusion (19%), and biceps tendinitis (13%). Although US abnormalities were most frequent in patients with painful shoulders or abnormal findings on physical examination or radiography, a high rate of alterations was found in asymptomatic shoulders (51%), in normal shoulders on physical examination (44%) and in normal shoulders on radiographic assessment (61%). Differences of US findings in relation to time of evolution of rheumatoid arthritis, patient's age, and radiographic stage in hand and/or wrist joints were not found. CONCLUSION: US abnormalities in the shoulder joint are frequent in rheumatoid arthritis, both in patients with and without shoulder complaints as well as in patients with normal findings on physical examination.

Naranjo A, Ojeda S, Francisco F, Erausquin C, Rúa-Figueroa I, Rodríguez-Lozano C. · No affiliation provided · Ann Rheum Dis. · Pubmed #12079919 links to  free full text

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