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ID PMID Title PublicationDate abstract
23750901 The nurse's role in addressing unmet treatment and management needs of patients with rheum 2013 Jun PURPOSE: Evaluate nurse's role in management of patients with rheumatoid arthritis (RA). METHODS: Modified Delphi with two rounds of questionnaires, followed by in-person meeting. International group of 12 nurses experienced with RA patients receiving biologic therapy. FINDINGS: Nurses often spend more time with patients than doctors do. Nurse is in unique position to explore patient needs; educate about treatment, administration, product storage, and self-injection technique; determine readiness for and understanding of treatment; monitor safety and progress; and coordinate care within multidisciplinary setting. CONCLUSIONS: Nurse's role is complex and vitally important to optimal RA patient care. Additional nurse involvement may address unmet needs. IMPLICATIONS FOR NURSING PRACTICE: Rheumatology nurses can address unmet patient needs by expanding current roles and by adopting additional functions.
23328930 Resveratrol inhibits TNF-α-induced IL-1β, MMP-3 production in human rheumatoid arthritis 2013 Jul Resveratrol (trans-3,4'-trihydroxystilbene), a natural phytoalexin, possesses anti-inflammatory, anti-proliferative, and immunomodulatory properties and has the potential for treating inflammatory disorders. The present study was designed to investigate the effects of resveratrol on TNF-α-induced inflammatory cytokines production of IL-1β and MMP3 in Rheumatoid arthritis (RA) Fibroblast-like synoviocytes (FLS) and further to explore the role of PI3K/Akt signaling pathway by which resveratrol modulates those cytokines production. The levels of IL-1β, MMP-3 in cultural supernatants among groups were measured by enzyme-linked immunosorbent assay. Messenger RNA expression of IL-1β and MMP-3 in RA FLS was analyzed using a reverse transcription-polymerase chain reaction. Western blot analysis was used to detect proteins expression in RA FLS intervened by resveratrol. Resveratrol inhibited both mRNA and proteins expressions of IL-1β and MMP-3 on RA FLS in a dose-dependent manner. Resveratrol also decreased significantly the expression of phosphorylated Akt dose dependently. Activation of PI3K/Akt signaling pathway exists in TNF-α-induced production of IL-1β and MMP3 on RA FLS, which is hampered by PI3K inhibitor LY294002. Immunofluorescence staining showed that TNF-α alone increased the production of P-Akt, whereas LY294002 and 50 μM resveratrol suppressed the TNF-α-stimulated expression of P-Akt. Resveratrol attenuates TNF-α-induced production of IL-1β and MMP-3 via inhibition of PI3K-Akt signaling pathway in RA FLS, suggesting that resveratrol plays an anti-inflammatory role and might have beneficial effects in preventing and treating RA.
25482151 Increased proteasome activator 28 gamma (PA28γ) levels are unspecific but correlate with 2014 Dec 8 BACKGROUND: PA28γ (also known as Ki, REG gamma, PMSE3), a member of the ubiquitin-and ATP-independent proteasome activator family 11S, has been proved to show proteasome-dependent and -independent effects on several proteins including tumor suppressor p53, cyclin-dependent kinase inhibitor p21 and steroid receptor co-activator 3 (SCR-3). Interestingly, PA28γ is overexpressed in pathological tissue of various cancers affecting e. g. breast, bowl and thyroids. Furthermore, anti-PA28γ autoantibodies have been linked to several autoimmune disorders. The aim of this study was to develop and evaluate a novel and sensitive PA28γ sandwich ELISA for the quantification of PA28γ serum levels in patients with cancer and autoimmune diseases for diagnostic and prognostic purposes. METHODS: PA28γ-specific polyclonal antibodies and recombinant His-tagged PA28γ were purified and used to develop a sandwich ELISA for the detection of circulating PA28γ. With this new assay, PA28γ serum levels of patients with various cancers, rheumatoid arthritis (RA), Sjögren's syndrome (SS), adult-onset Still's disease (AOSD) and different connective-tissue diseases (CTD) were compared with healthy control subjects. Anti-PA28γ autoantibodies were additionally confirmed using a newly developed microbead assay. RESULTS: The developed PA28γ sandwich ELISA showed a high specificity with a detection limit of 3 ng/ml. A significant up-regulation of circulating PA28γ was detected in the sera of patients with cancer, RA, SS and CTD. A significant correlation was observed dependent on age as well as anti-PA28γ autoantibody levels with circulating PA28γ protein levels. Furthermore, PA28γ serum levels showed a correlation with disease activity in patients with RA under treatment with the T-cell directed biological compound abatacept according to disease activity score 28 (DAS28) and erythrocyte sedimentation rate (ESR). CONCLUSION: The application of PA28γ as a novel biomarker for diagnostic purposes of a specific disease is limited, since elevated levels were observed in different disorders. However, the correlation with disease activity in patients with RA suggests a prognostic value, which needs to be addressed by further studies. Therefore our results show that PA28γ is a useful marker which should be included in studies related to novel treatments, e.g. abatacept.
24641720 The psychophysiological stress response in psoriasis and rheumatoid arthritis. 2014 Apr BACKGROUND: Psychosocial stress can be a risk factor for the maintenance and exacerbation of chronic inflammatory diseases, such as psoriasis and rheumatoid arthritis (RA). OBJECTIVES: To gain insight into the specificity of the psychophysiological stress response during chronic inflammation, we assessed autonomic and neuroendocrine responses to stress in different chronic inflammatory diseases. METHODS: Thirty patients with psoriasis (nine women, mean age 58·5 years ± 12·4), 34 patients with RA (16 women, mean age 60·8 years ± 9·2) and 25 healthy controls (16 women, mean age 55·6 years ± 8·7) underwent a standardized psychosocial stress task (Trier Social Stress Test). Salivary levels of α-amylase and cortisol and self-reported tension levels were measured before and after the stress test. RESULTS: The cortisol response to stress was heightened in patients with psoriasis compared with patients with RA and healthy controls, whereas there were no differences in the autonomic and self-reported measures. CONCLUSIONS: The altered neuroendocrine stress response in patients with psoriasis suggests that stressful events might have different physiological consequences for specific patient groups with chronic inflammatory conditions, possibly adversely affecting disease status.
24019095 Mid-term results of computer-assisted cervical reconstruction for rheumatoid cervical spin 2013 Nov STUDY DESIGN: A retrospective single-center study. We routinely have used C1-C2 transarticular and cervical pedicle screw fixations to reconstruct highly destructed unstable rheumatoid arthritis (RA) cervical lesions. However, there is little data on mid-term results of surgical reconstruction for rheumatoid cervical disorders, particularly, cervical pedicle screw fixation. OBJECTIVES: The purpose of this study was to evaluate the mid-term surgical results of computer-assisted cervical reconstruction for such lesions. METHODS: Seventeen subjects (4 men, 13 women; mean age, 61 ± 9 years) with RA cervical lesions who underwent C1-C2 transarticular screw fixation or occipitocervical fixation, with at least 5 years follow-up were studied. A frameless, stereotactic, optoelectronic, CT-based image-guidance system, was used for correct screw placement. Variables including the Japanese Orthopaedic Association (JOA) score, Ranawat class, EuroQol (EQ-5D), atlantodental interval, and Ranawat values before, and at 2 and 5 years after surgery, were evaluated. Furthermore, screw perforation rates were evaluated. RESULTS: The lesions included atlantoaxial subluxation (AAS, n = 6), AAS + vertical subluxation (VS, n = 7), and AAS + VS + subaxial subluxation (n = 4). There was significant neurological improvement at 2 years after surgery, as evidenced by the JOA scores, Ranawat class, and the EQ-5D utility weight. However, at 5 years after surgery, there was a deterioration of this improvement. The Ranawat values before, and at 2 and 5 years after surgery, were not significantly different. Major screw perforation rate was 2.1 %. No neural and vascular complications associated with screw insertion were observed. CONCLUSIONS: Subjects with rheumatoid cervical lesions who underwent C1-C2 transarticular screw fixation or occipitocervical fixation using a pedicle screw had significantly improved clinical parameters at 2 years after surgery. However, there was a deterioration of this improvement at 5 years post surgery.
23233117 -174G/C interleukin-6 gene promoter polymorphism predicts therapeutic response to etanerce 2013 Jun To examine whether -174G/C interleukin-6 (IL-6) gene polymorphism, previously reported to correlate with IL-6 level, influences response to etanercept therapy in patients with rheumatoid arthritis. Seventy-seven patients with active RA were studied, at baseline and 6- and 12-month follow-up after etanercept therapy. Treatment response was estimated according to the European League Against Rheumatism response criteria. RA patients were genotyped for -174G/C IL-6 gene polymorphism by the PCR-RFLP method, and influence of genotype at this polymorphism to clinical response to etanercept was assessed. After 12 months of treatment, the percentage of responders (patients who had DAS28 improvement >1.2) was significantly increased in patients carrying the IL-6 -174G/G genotype (95.7 %) compared with those with the G/C (75.6 %) or CC (44.4 %) genotype (p = 0.006 by Chi-square test). No significant difference in the mean values of DAS28 improvement was observed between groups with different genotype. RA patients with an IL-6 -174GG genotype respond to etanercept better than patients with GC or CC genotype. This finding, if confirmed in future studies, suggests that the -174G/C IL-6 polymorphism may be a genetic marker of responsiveness to tumor necrosis factor-alpha (TNF-α) blockers in RA.
23925980 Lipid and lipoprotein levels and trend in rheumatoid arthritis compared to the general pop 2013 Dec OBJECTIVE: Differences in lipid levels associated with cardiovascular (CV) risk between rheumatoid arthritis (RA) patients and the general population remain unclear. Determining these differences is important in understanding the role of lipids in CV risk in RA. METHODS: We studied 2,005 RA subjects from 2 large academic medical centers. We extracted electronic medical record data on the first low-density lipoprotein (LDL) measurement, and total cholesterol and high-density lipoprotein (HDL) measurements within 1 year of the LDL measurement. Subjects with an electronic statin prescription prior to the first LDL measurement were excluded. We compared lipid levels in RA patients to recently published levels from the general US population using the t-test and stratifying by published parameters, i.e., 2007-2010, and women. We determined lipid trends using separate linear regression models for total cholesterol, LDL cholesterol, and HDL cholesterol, testing the association between year of measurement (1989-2010) and lipid level, adjusted by age and sex. Lipid trends in RA were qualitatively compared to the published general population trends. RESULTS: Women with RA had a significantly lower total cholesterol (186 versus 200 mg/dl; P = 0.002) and LDL cholesterol (105 versus 118 mg/dl; P = 0.001) compared to the general population (2007-2010). HDL cholesterol was not significantly different in the 2 groups. In the RA cohort, total cholesterol and LDL cholesterol significantly decreased each year, while HDL cholesterol increased (all with P < 0.0001), consistent with overall trends observed in a previous study. CONCLUSION: RA patients appear to have an overall lower total cholesterol and LDL cholesterol than the general population despite the general overall risk of CV disease in RA from observational studies.
24609059 Mitochondrial dysfunction promotes and aggravates the inflammatory response in normal huma 2014 Jul OBJECTIVES: In RA, synoviocytes cause increased oxidative stress, leading to mitochondrial alterations that may participate in the pathogenesis of RA. Here we investigated whether mitochondrial dysfunction induces inflammatory responses in cultured normal human synoviocytes, a hallmark of RA. METHODS: Mitochondrial dysfunction was induced with the inhibitor oligomycin. The effects of mitochondrial dysfunction on cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and IL-8 expression; cellular and mitochondrial reactive oxygen species (ROS) production; nuclear factor-κB (NF-κB) activation and p65 translocation were studied. ROS scavengers (N-acetylcysteine and mitoTEMPO) and an NF-κB inhibitor (BAY-117085) were used to investigate the pathways involved. The natural anti-inflammatory antioxidant resveratrol was also tested. RESULTS: Mitochondrial dysfunction per se significantly stimulated mitochondrial ROS production as well as low-grade expressions of COX-2, PGE2 and IL-8. Interestingly, mitochondrial dysfunction induced by pretreatment of synoviocytes with oligomycin synergized with IL-1β to increase the expression of these inflammatory mediators. The inflammatory effects of mitochondrial damage appeared to be dependent on ROS production and NF-κB activation since the inflammatory response was counteracted by both N-acetylcysteine and mitoTEMPO and it was also reduced by BAY-117085. Antimycin A and paraquat (inhibitors of mitochondrial function) also induced inflammatory responses. Furthermore, resveratrol significantly reduced the inflammatory response by decreasing ROS production and NF-κB activation. CONCLUSION: These data suggest that mitochondrial dysfunction could induce an inflammatory response in normal human synoviocytes and sensitize these cells, causing a significant amplification of the inflammatory response induced by IL-1β. Resveratrol may represent a promising strategy in controlling the synovial inflammatory response.
24577818 The performance of a point of care test for detection of anti-mutated citrullinated viment 2014 Jul The purpose of this study was to determine the diagnostic performance of a point-of-care test (POCT) for detection of anti-mutated citrullinated vimentin (anti-MCV) and rheumatoid factor (RF) in early rheumatoid arthritis (RA) with 2 years of disease duration or less. Additionally, we evaluated the agreement of these tests when using EDTA whole blood and capillary blood. Patients with RA and other rheumatic disorders were consecutively recruited from the rheumatology outpatient clinic. The POCT for detection of anti-MCV and RF using capillary blood and EDTA whole blood was performed in 78 patients with early RA, 55 patients with other rheumatic disorders, and 55 healthy blood donors. The sensitivity and specificity of anti-MCV POCT in patients with early RA were 64 and 97 %, respectively, while the sensitivity and specificity of RF POCT were 51 and 95 %, respectively. The positive likelihood ratio of the POCT for anti-MCV was higher than those for RF (23.5 vs 9.4). The negative likelihood was 0.37 for anti-MCV and 0.52 for RF. There were three cases with false positive for anti-MCV including a patient with psoriatic arthritis and the other two with systemic sclerosis. The agreement between capillary blood and EDTA whole blood testing for anti-MCV and RF was low to moderate with Cohen's kappa of 0.58 and 0.49, respectively. This POCT for detection of anti-MCV and RF yielded high specificity and may be a valuable tool for the diagnosis of early RA. Using this POCT with EDTA whole blood instead of capillary blood is not recommended.
25294249 Isotretinoin-induced arthritis mimicking both rheumatoid arthritis and axial spondyloarthr 2015 May Isotretinoin is used for the treatment of various acne lesions that are resistant to other treatments. The most frequent rheumatologic side effect of isotretinoin is transient muscle and/or joint pains. Here, we report a case with bilateral wrist and metacarpophalangeal joint arthritis and unilateral sacroiliitis associated with isotretinoin usage to attract attention, particularly from physiatrists, rheumatologists and dermatologists, to this rare adverse effect of isotretinoin.
25182696 The perplexity of prescribing and switching of biologic drugs in rheumatoid arthritis: a U 2014 Sep 2 BACKGROUND: Biologic drugs are expensive treatments used in rheumatoid arthritis (RA). Switching among them is common practice in patients who have had an inadequate response or intolerable adverse events. The National Institute of Health and Clinical Excellence (NICE) UK, which aims to curtail postcode prescribing, has provided guidance on the sequential prescription of these drugs. This study sought to evaluate the extent to which rheumatology centres across the Midlands were complying with NICE guidance on the switching of biologic drugs in RA, as well as analyse the various prescribing patterns of these drugs. METHODS: Data was collected via a web-based tool on RA patients who had undergone at least one switch of a biologic drug during 2011. The standards specified in NICE technology appraisals (TA130, TA186, TA195, TA198, and TA225) were used to assess compliance with NICE guidance. Descriptive statistical analysis was performed. RESULTS: There were 335 biologic drug switches in 317 patients. The most common reason given for switching to a drug was NICE guidelines (242, 72.2%), followed by Physician's choice (122, 33.4%). Lack of effect was the most common reason for discontinuing a drug (224, 67%). For patients on Rituximab, Methotrexate was used in 133 switches (76.9% of the time). Overall NICE compliance for all units was 65% (range 50 to 100%), with anti-TNFα to anti-TNFα switches for inefficacy making up the majority of non-compliant switches. CONCLUSION: This study draws attention to the enigma and disparity of commissioning and prescribing of biologic drugs in RA. Currently the evidence would not support switching of a biologic drug for non-clinical purposes such as economic pressures. Flexibility in prescribing should be encouraged: biologic therapy should be individualised based on the mode of action and likely tolerability of these drugs. Further work should focus on the evidence for using particular sequences of biologic drugs.
23742043 Leflunomide discontinuation in rheumatoid arthritis and influence of associated disease-mo 2013 OBJECTIVES: The aims of this study were to describe the rate of leflunomide discontinuation in rheumatoid arthritis (RA) patients, in standard clinical practice, and to analyse which factors could influence this rate, paying particular attention to the concomitant treatment with other disease-modifying anti-rheumatic drugs (DMARDs). METHOD: We selected RA patients, diagnosed according to the 1987 American College of Rheumatology (ACR) criteria, attending the rheumatology outpatient clinic of the San Carlos Clinical Hospital (Madrid, Spain), who had started treatment with leflunomide between 1 January 2006 and 1 January 2011. Clinical records were examined until withdrawal of the drug, loss of follow-up, or 1 October 2011. Kaplan-Meier curves were set to account for leflunomide withdrawal. Cox bivariate and multivariate regression models were conducted to examine risk factors for leflunomide discontinuation. RESULTS: The incident rate (IR) for leflunomide discontinuation, regardless of the cause, was 27 per 100 patient-years [95% confidence interval (CI) 22-31]. We observed, in both the bivariate and multivariate regression analysis, that those aged > 75 years at the start of the leflunomide treatment and undergoing concurrent treatment with methotrexate (MTX) and/or hydroxychloroquine (HC) had a significantly higher risk of leflunomide discontinuation. CONCLUSIONS: An older age at the start of the treatment with leflunomide, or concomitant treatment with MTX and/or HC, could be associated with a higher risk of leflunomide discontinuation, regardless of the cause. Therefore, when taking MTX or HC, patients receiving leflunomide should be closely monitored early to detect the occurrence of adverse reactions, and hence prevent their aggravation.
23644115 [Value of four serum markers in the diagnosis of rheumatoid arthritis]. 2013 Apr OBJECTIVE: To systematically evaluate the values of 4 serum markers in the diagnosis of rheumatoid arthritis (RA). METHODS: Serum samples were obtained from 278 RA patients and 510 control subjects and the levels of rheumatoid factor (RF), anticyclic citrullinated peptide antibody (CCP), antikeratin antibody (AKA), and glucose-6-phosphate isomerase (GPI) were detected using immune turbidimetry, ELISA, indirect immunofluorescence, and ELISA, respectively. The values of these 4 serum markers and their combinations in RA diagnosis were systemically assessed. RESULTS: In RA diagnosis using one serum marker, two markers, and three or four markers, RF, RF+CCP, RF+CCP+GPI, respectively, had the highest sensitivity; CCP, CCP+AKA, and RF+CCP+AKA+GPI, respectively, had the highest specificity; CCP, CCP+GPI, and RF+CCP+AKA+GPI, respectively, had the highest positive predictive value; GPI, RF+CCP, and RF+CCP+GPI, respectively, had the highest negative predictive value; CCP, CCP+GPI, and RF+CCP+AKA+GPI, respectively, had the highest positive likely ratio; GPI, RF+CCP, and RF+CCP+GPI, respectively, had the lowest negative likely ratio. CONCLUSION: CCP, RF+CCP, and RF+CCP+GPI are the most ideal for RA diagnosis using one, two, and three or more markers, respectively. CCP is the essential marker for RA diagnosis, and a combined detection of the serum makers can significantly improve the diagnostic accuracy.
25433021 Cardiovascular disease in patients with chronic inflammation: mechanisms underlying premat 2015 Feb 21 A variety of systemic inflammatory rheumatic diseases associate with an increased risk of atherosclerotic events and premature cardiovascular (CV) disease. Although this recognition has stimulated intense basic science and clinical research, the precise nature of the relationship between local and systemic inflammation, their interactions with traditional CV risk factors, and their role in accelerating atherogenesis remains unresolved. The individual rheumatic diseases have both shared and unique attributes that might impact CV events. Understanding of the positive and negative influences of individual anti-inflammatory therapies remains rudimentary. Clinicians need to adopt an evidence-based approach to develop diagnostic techniques to identify those rheumatologic patients most at risk of CV disease and to develop effective treatment protocols. Development of optimal preventative and disease-modifying approaches for atherosclerosis in these patients will require close collaboration between basic scientists, CV specialists, and rheumatologists. This interface presents a complex, important, and exciting challenge.
22173958 The effectiveness of Echinacea extract or composite glucosamine, chondroitin and methyl su 2013 Mar The study aimed to investigate the effect of the oral administration for 15 days of either Echinacea (E) or genuphil (a composite of chondroitin sulphate, glucosamine and methyl sulfonyl methane [GCM]) nutraceutical supplements on female rat model of acute or chronic arthritis induced by bacterial outer membrane protein (OMP) from faecal flora of healthy and rheumatic humans. Anti-cyclic citrullinated peptide (anti-CCP2), C-reactive protein (CRP) and rheumatoid factor (RF) values increased (p < 0.05) in both arthritic groups as compared to normal values. The rheumatic markers anti-CCP2, CRP and RF values decreased significantly in E- and GCM-treated groups compared to arthritic none-treated acute or chronic groups. The results of RF values of GCM-treated groups in acute and chronic models decreased exhibiting no statistical difference compared with the normal value. Histological examinations of the hind paw sections revealed moderate inflammation, oedema and mild proliferation of synovial cells in acute arthritic rats and more damage to cartilage and bone with severe inflammation in chronic ones. Echinacea acute treated group showed edema with proliferated synovial membrane and partial damage in cartilage and bone. While in the E-chronic treated group, rough edge with destructed cartilage and bone existed. However, the acute GCM group revealed mild cartilage damage. But the chronic GCM group showed mild synovial cells proliferation and revealed no inflammation with mild cartilage damage edge. Results demonstrated the OMP arthropathic property and through promising light on arthritis treatment using E- or GCM, with the advantage of GMC results over that of E-. The composite GCM is needed for further studies over the dose and duration to assess its preventive effects against the bacterial OMP arthrogenicity.
23728274 Periodontal therapy in chronic periodontitis lowers gingival crevicular fluid interleukin- 2013 Oct To evaluate clinical outcomes and effects of non-surgical periodontal therapy on serum, gingival crevicular fluid (GCF) interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels in chronic periodontitis patients with/without rheumatoid arthritis (RA), fifteen RA patients with chronic periodontitis (RA-P) and 15 systemically healthy non-RA chronic periodontitis patients (H-P) were recruited. Clinical periodontal recordings, GCF, and blood samples were obtained at baseline, 1, 3, and 6 months after periodontal treatment. GCF, serum IL-1β, TNF-α levels were analyzed by ELISA. Disease activity score 28 (DAS28) was used to assess RA clinical morbidity. Study groups were compared by Mann-Whitney U test. Wilcoxon test was used to compare the data at baseline, 1, 3, and 6 months after periodontal therapy within the same group. DAS28 decreased significantly after periodontal therapy in RA-P group (p < 0.01). Serum TNF-α concentrations of H-P group were significantly higher than those of RA-P group (p < 0.01), whereas IL-1β levels were similar. No significant change was observed in serum levels of these cytokines after periodontal therapy. GCF IL-1β amounts decreased significantly in both groups following treatment (p < 0.01). At 6-months, H-P GCF IL-1β concentrations were significantly lower than baseline. DAS28 and GCF IL-1β correlated with clinical periodontal indices (p < 0.01). Significant decreases in DAS28 and GCF IL-1β amounts after periodontal treatment suggest that periodontal therapy synergizes with systemic RA therapy to improve RA status.
23281295 Incidence and time trends of herpes zoster in rheumatoid arthritis: a population-based coh 2013 Jun OBJECTIVE: To determine the incidence, time trends, risk factors, and severity of herpes zoster in a population-based cohort of patients with newly diagnosed rheumatoid arthritis (RA) compared to a group of individuals without RA from the same population. METHODS: All residents of Olmsted County, Minnesota fulfilling for the first time the 1987 American College of Rheumatology criteria for RA between January 1, 1980 and December 31, 2007 and a cohort of similar residents without RA were assembled and followed by retrospective chart review until death, migration, or December 31, 2008. RESULTS: There was no difference in the presence of herpes zoster prior to the RA incidence/index date between the cohorts (P = 0.85). During followup, 84 patients with RA (rate 12.1 cases per 1,000 person-years) and 44 subjects without RA (rate 5.4 cases per 1,000 person-years) developed herpes zoster. Patients with RA were more likely to develop herpes zoster than those without RA (hazard ratio [HR] 2.4 [95% confidence interval (95% CI) 1.7-3.5]). Herpes zoster occurred more frequently in patients diagnosed with RA more recently (HR 1.06 per year [95% CI 1.02-1.10]). Erosive disease, previous joint surgery, and use of hydroxychloroquine and corticosteroids were significantly associated with the development of herpes zoster in RA. There was no apparent association of herpes zoster with the use of methotrexate or biologic agents. Complications of herpes zoster occurred at a similar rate in both cohorts. CONCLUSION: The incidence of herpes zoster is increased in RA and has risen in recent years. There also has been an increasing incidence of herpes zoster in more recent years in the general population. RA disease severity is associated with the development of herpes zoster.
24983251 Epi2Loc: an R package to investigate two-locus epistatic models. 2014 Aug Epistasis is a growing area of research in genome-wide studies, but the differences between alternative definitions of epistasis remain a source of confusion for many researchers. One problem is that models for epistasis are presented in a number of formats, some of which have difficult-to-interpret parameters. In addition, the relation between the different models is rarely explained. Existing software for testing epistatic interactions between single-nucleotide polymorphisms (SNPs) does not provide the flexibility to compare the available model parameterizations. For that reason we have developed an R package for investigating epistatic and penetrance models, Epi2Loc, to aid users who wish to easily compare, interpret, and utilize models for two-locus epistatic interactions. Epi2Loc facilitates research on SNP-SNP interactions by allowing the R user to easily convert between common parametric forms for two-locus interactions, generate data for simulation studies, and perform power analyses for the selected model with a continuous or dichotomous phenotype. The usefulness of the package for model interpretation and power analysis is illustrated using data on rheumatoid arthritis.
23801380 Association of the IRF5 rs2004640 polymorphism with rheumatoid arthritis: a meta-analysis. 2013 Nov Several molecular epidemiological studies have been conducted in recent years to evaluate a possible association between the interferon regulatory factor 5 (IRF5) rs2004640 polymorphism and rheumatoid arthritis risk in diverse populations. However, the results remain conflicting rather than conclusive. Our aim was to assess associations of IRF5 gene polymorphisms with rheumatoid arthritis risk. Meta-analysis was performed on six published case-control studies (from eight countries) that included 4,818 cases of rheumatoid arthritis and 4,316 controls. The rs2004640-T allele was associated with a significantly increased risk of rheumatoid arthritis when the dominant genetic model was applied (T/T + T/G versus G/G: P = 0.003, OR = 1.14, 95% CI 1.05-1.25). Upon stratified analysis by ethnicity, the rs2004640 polymorphism was associated with an increased rheumatoid arthritis risk in Caucasians when the homozygotic contrast model was employed(T/T versus G/G: P = 0.03, OR = 1.25, 95% CI 1.02-1.53) and this was also the case when the dominant genetic model was used (T/T + T/G versus G/G: P = 0.04, OR = 1.20, 95% CI 1.01-1.42), whereas, in Asian populations, only the dominant genetic model was associated with an increased rheumatoid arthritis risk (T/T + T/G versus G/G: P = 0.02, OR = 1.14, 95% CI 1.02-1.26). The results suggest that the IRF5 rs2004640 polymorphism is associated with rheumatoid arthritis especially when the dominant genetic model is applied.
25068378 Single nucleotide polymorphism of RANKL and OPG genes may play a role in bone and joint in 2014 Sep OBJECTIVES: This paper aims to investigate the influence of single-nucleotide polymorphisms (SNPs) in the receptor of activator of nuclear factor kappaB ligand (RANKL) gene (TNFSF11) and osteoprotegerin (OPG) gene (TNFRSF11B) on bone and joint injury in patients with rheumatoid arthritis (RA). METHODS: Two hundred RA patients and 201 matched controls were analysed by case-control design, and their samples were genotyped. Bone mineral density (BMD) and serum OPG and RANKL levels were measured. Clinical and laboratory parameters were recorded, and the radiographic changes in both hands of RA were evaluated by Sharp's method. RESULTS: Our results showed no significant differences in the distribution frequency of the alleles and genotypes of TNFRSF11B (rs2073618 and rs3102735) and TNFSF11 (rs2277438) between the RA group and controls (p>0.05). Compared to patients with TNFSF11 (rs2277438) AA or GG genotype, RA with TNFSF11 (rs2277438) AG genotype had significantly decreased BMD values at lumbar spine 3, lumbar spine 4, lumbar spine 2-4 (p<0.05-0.01), and apparently elevated Sharp scores (p<0.05), respectively. The RA group showed significantly higher serum levels of RANKL, RANKL/OPG ratio and a lower serum level of OPG than that of the controls (p<0.05-0.0001). RA patients with RANKL-rs2277438 heterozygotic genotype (AG) had significantly increased serum levels of RANKL (p<0.05), compared to homozygotic genotype (AA or GG). CONCLUSIONS: These results indicate that SNP of TNFRSF11B (rs2073618 and rs3102735) and TNFSF11 (rs2277438) may not be susceptibility factors for RA in Chinese Han population. SNP of TNFSF11 (rs2277438) may have an important influence on bone and joint injury in RA.