Meta-analysis of associations between functional HLA-G polymorphisms and susceptibility to systemic lupus erythematosus and rheumatoid arthritis.

The aim of this study was to determine whether the functional HLA-G 14 bp insertion (I)/deletion (D) and +3142 G/C polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the HLA-G 14 bp I/D, and +3142 G/C polymorphisms and SLE or RA using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) additive model. A total of 14 comparison studies from 11 articles met our inclusion criteria, comprising eight on SLE (1,284 patients and 1,885 controls) and four on RA (820 patients and 772 controls), and three studies investigated response to methotrexate (MTX) in RA according to the HLA-G 14 bp I/D polymorphisms (249 responders and 205 nonresponders).

Association between the functional ITGAM rs1143679 G/A polymorphism and systemic lupus erythematosus/lupus nephritis or rheumatoid arthritis: an update meta-analysis.

The aim of this study was to determine whether the functional integrin-α-M (ITGAM) rs1143679 polymorphism is associated with susceptibility to systemic lupus erythematosus (SLE), lupus nephritis (LN), and rheumatoid arthritis (RA). A series of meta-analyses were conducted to test for associations between the ITGAM rs1143679 polymorphism and SLE, LN, or RA. A total of 24 comparisons involving 7,738 patients and 8,309 controls for SLE, and 2,663 patients and 2,694 controls in RA were considered.

Prevalence, incidence, and associated factors of avascular necrosis in Korean patients with systemic lupus erythematosus: a nationwide epidemiologic study.

Avascular necrosis (AVN) is one of the most frequent types of organ damage in systemic lupus erythematosus (SLE). However, little is currently known about the epidemiology of AVN in SLE patients. The aim of this study was to estimate the prevalence and incidence of AVN in Korean patients with SLE based on National Health Insurance (NHI) claims data and to determine the risk factors for AVN among SLE patients.

Targeted exon sequencing fails to identify rare coding variants with large effect in rheumatoid arthritis.

Introduction: Although it has been suggested that rare coding variants could explain the substantial missing heritability, very few sequencing studies have been performed in rheumatoid arthritis (RA). We aimed to identify novel functional variants with rare to low frequency using targeted exon sequencing of RA in Korea.

Methods: We analyzed targeted exon sequencing data of 398 genes selected from a multifaceted approach in Korean RA patients (n = 1,217) and controls (n = 717).

Efficacy and safety of tofacitinib for active rheumatoid arthritis with an inadequate response to methotrexate or disease-modifying antirheumatic drugs: a meta-analysis of randomized controlled trials.

Background/aims: The aim of this study was to assess the efficacy and safety of tofacitinib (5 and 10 mg twice daily) in patients with active rheumatoid arthritis (RA).

Methods: A systematic review of randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib in patients with active RA was performed using the Medline, Embase, and Cochrane Controlled Trials Register databases as well as manual searches.

Results: Five RCTs, including three phase-II and two phase-III trials involving 1,590 patients, met the inclusion criteria.

The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.

Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls.

Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA.

Objectives: Systemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (CR2/CD21) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association.

Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations.

Previous studies have emphasized ethnically heterogeneous human leukocyte antigen (HLA) classical allele associations to rheumatoid arthritis (RA) risk. We fine-mapped RA risk alleles within the major histocompatibility complex (MHC) in 2782 seropositive RA cases and 4315 controls of Asian descent. We applied imputation to determine genotypes for eight class I and II HLA genes to Asian populations for the first time using a newly constructed pan-Asian reference panel.

Are glucocorticoid-induced osteoporosis recommendations sufficient to determine antiosteoporotic treatment for patients with rheumatoid arthritis?

Background/aims: We investigated differences in identifying candidates for antiosteoporotic treatment in rheumatoid arthritis (RA) patients according to two available clinical guidelines.

Methods: We prospectively enrolled 100 female patients aged 50 years or older with RA who visited Hanyang University Hospital for periodic examinations between April 2011 and August 2011. We applied the glucocorticoid-induced osteoporosis (GIOP) recommendations and the National Osteoporosis Foundation (NOF) guidelines to RA patients and examined agreement between the guidelines for identifying candidates for antiosteoporotic treatment.

Improving participation in clinical trials of novel therapies: going back to basics.

Clinical trials in many diseases are experiencing more difficulties in achieving sufficient or timely enrollment of participants; anecdotal reports from trials of novel therapies for systemic lupus erythematosus (SLE) seem to be facing the same challenges. General factors associated with this trend include the growth of the contract research industry, increasing oversight, and high-profile accounts of scientific misconduct and fraud in research. Complicated protocols that increase participant burden, overly restrictive entry criteria, the fear of an SLE flare may also affect enrollment in SLE trials.

The influence of vertebral fracture on the functional disability of patients with rheumatoid arthritis.

The aim of the present study was to identify the influence of vertebral fracture (VF) on the functional disability in patients with rheumatoid arthritis (RA). This study consecutively enrolled 100 female patients aged 50 yr or older with RA. All participants underwent lateral imaging of the thoracolumbar spine by simple radiography to identify any VFs.

Liver X receptors alpha gene (NR1H3) promoter polymorphisms are associated with systemic lupus erythematosus in Koreans.

Introduction: Liver X receptors are established sensors of lipid and cholesterol homeostasis. Recent studies have reported that these receptors are involved in the regulation of inflammation and immune responses. We attempted to identify single nucleotide polymorphisms (SNPs) of the NR1H3 gene associated with the susceptibility to systemic lupus erythematosus (SLE).

Electrocardiographic findings in systemic lupus erythematosus: data from an international inception cohort.

Objective: To estimate the early prevalence of various electrocardiographic (EKG) abnormalities in patients with systemic lupus erythematosus (SLE) and to evaluate possible associations between repolarization changes (increased corrected QT [QTc] and QT dispersion [QTd]) and clinical and laboratory variables, including the anti-Ro/SSA level and specificity (52 or 60 kd).

Methods: We studied adult SLE patients from 19 centers participating in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Registry. Demographics, disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K]), disease damage (SLICC/American College of Rheumatology Damage Index [SDI]), and laboratory data from the baseline or first followup visit were assessed.

Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort.

Background And Aims: We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients.

Methods: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model.

Association of the MTHFR C677T and A1298C polymorphisms with methotrexate toxicity in rheumatoid arthritis: a meta-analysis.

The aim of this study was to explore whether the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) play a role in methotrexate (MTX) toxicity in rheumatoid arthritis (RA). MEDLINE and EMBASE database searches and subsequent manual searches were utilized to identify articles in which C677T and A1298C MTHFR polymorphisms were evaluated in RA patients taking MTX. A meta-analysis was conducted to identify associations between MTHFR polymorphisms and MTX toxicity.

Associations between functional TNFR2 196 M/R polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis.

Several studies have examined the effects of tumor necrosis factor receptor (TNFR) 1 +38 A/G and TNFR2 196 M/R polymorphisms on susceptibility to RA and have reported conflicting results. The purpose of this study was to examine whether the TNFR1 +38 A/G and TNFR2 196 M/R polymorphisms are associated with RA susceptibility. We performed a literature search using the Medical Literature Analysis and Retrieval System Online and Embase citation indices, and conducted a meta-analysis to examine the association between the TNFR1 +38 A/G and TNFR2 196 M/R polymorphisms and RA.

Coffee or tea consumption and the risk of rheumatoid arthritis: a meta-analysis.

Meta-analysis of the cohort studies revealed a trend of an association between total coffee intake and RA incidence (RR of the highest vs. the lowest group = 1.309, 95 % confidence interval [CI] = 0.

Functional FCGR3A 158 V/F and IL-6 -174 C/G polymorphisms predict response to biologic therapy in patients with rheumatoid arthritis: a meta-analysis.

The aim of this study was to investigate whether the Fc gamma receptor 3A (FCGR3A) 158 V/F and interleukin-6 (IL-6) promoter -174 G/C polymorphisms can predict the response to biologic-based therapy in patients with rheumatoid arthritis (RA). We conducted a meta-analysis of studies on the association between the FCGR3A V/F polymorphism or the IL-6 -174 C/G polymorphism and non-responsiveness to biologic therapy in RA patients. A total of 10 studies involving 1,427 patients were considered.

Two functional lupus-associated BLK promoter variants control cell-type- and developmental-stage-specific transcription.

Efforts to identify lupus-associated causal variants in the FAM167A/BLK locus on 8p21 are hampered by highly associated noncausal variants. In this report, we used a trans-population mapping and sequencing strategy to identify a common variant (rs922483) in the proximal BLK promoter and a tri-allelic variant (rs1382568) in the upstream alternative BLK promoter as putative causal variants for association with systemic lupus erythematosus. The risk allele (T) at rs922483 reduced proximal promoter activity and modulated alternative promoter usage.

Meta-analysis of associations between the peroxisome proliferator-activated receptor-γ Pro12Ala polymorphism and susceptibility to nonalcoholic fatty liver disease, rheumatoid arthritis, and psoriatic arthritis.

Introduction: The purpose of this study was to examine whether a Proline (Pro)-to-Alanine (Ala) exchange at codon 12 (Pro12Ala) polymorphism of the peroxisome proliferator-activated receptor-gamma (PPARγ) is associated with susceptibility to nonalcoholic fatty liver disease (NAFLD), rheumatoid arthritis (RA), and psoriatic arthritis (PsA).

Methods: A meta-analysis was conducted on the association between the PPARγ Pro12Ala polymorphism and NAFLD, RA, and PsA.

Results: Nine studies, including five on NAFLD, two on RA, and two on PsA, were available for the meta-analysis consisting of 8082 cases and 3790 controls.

Impact of early disease factors on metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort.

Background: The metabolic syndrome (MetS) may contribute to the increased cardiovascular risk in systemic lupus erythematosus (SLE). We examined the association between MetS and disease activity, disease phenotype and corticosteroid exposure over time in patients with SLE.

Methods: Recently diagnosed (<15 months) patients with SLE from 30 centres across 11 countries were enrolled into the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort from 2000 onwards.

American College of Rheumatology criteria at inception, and accrual over 5 years in the SLICC inception cohort.

Objective: To determine the frequency of each American College of Rheumatology (ACR) criterion met at time of enrollment, and the increase in each of the criteria over 5 years.

Methods: In 2000 the Systemic Lupus International Collaborating Clinics (SLICC) recruited an international inception cohort of patients with systemic lupus erythematosus (SLE; ≥ 4 ACR criteria) who were followed at yearly intervals according to a standard protocol. Descriptive statistics were used to assess the total and cumulative number of ACR criteria met at each visit.

Gene-environmental interaction between smoking and shared epitope on the development of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: a meta-analysis.

Objective: The aim of this study was to determine the gene-environment interactions of smoking and shared epitope (SE) both separately and combined on anti-cyclic citrullinated peptide (CCP) antibodies in patients with rheumatoid arthritis (RA).

Methods: The literature was searched using the MEDLINE, EMBASE and Cochrane databases. A meta-analysis on the associations between tobacco exposure (TE) and/or SE and the development of anti-CCP antibodies in patients with RA was performed.

Meta-analysis of gene expression profiles to predict response to biologic agents in rheumatoid arthritis.

Our aim was to identify differentially expressed (DE) genes and biological processes that may help predict patient response to biologic agents for rheumatoid arthritis (RA). Using the INMEX (integrative meta-analysis of expression data) software tool, we performed a meta-analysis of publicly available microarray Gene Expression Omnibus (GEO) datasets that examined patient response to biologic therapy for RA. Three GEO datasets, containing 79 responders and 34 non-responders, were included in the meta-analysis.

The role of bone scintigraphy in the diagnosis of rheumatoid arthritis according to the 2010 ACR/EULAR classification criteria.

We aimed to investigate the role of bone scintigraphy (BS) in the diagnosis of rheumatoid arthritis (RA) as a supplement to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria. A total of 156 patients who underwent BS with screening laboratory to confirm RA were enrolled. We divided them into two groups according to the presence of arthritis upon the first physical examination, and evaluated the diagnostic validity of BS as an independent (BS only) or assistant diagnostic tool using the 2010 criteria (BS-assisted).