scholarly journals Association analysis of the CCL3L1 copy number locus by paralogue ratio test in Norwegian rheumatoid arthritis patients and healthy controls

2012 ◽  
Vol 13 (7) ◽  
pp. 579-582 ◽  
Author(s):  
G B N Nordang ◽  
D Carpenter ◽  
M K Viken ◽  
T K Kvien ◽  
J A L Armour ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Association Analysis ◽  
Copy Number ◽  
Ratio Test ◽  
Healthy Controls ◽  
Paralogue Ratio Test

Autosome-wide Copy Number Variation Association Analysis for Rheumatoid Arthritis Using the WTCCC High-density SNP Genotype Data

2011 ◽  
Vol 38 (5) ◽  
pp. 797-801 ◽  
Author(s):  
MOHAMMED UDDIN ◽  
MITCH STURGE ◽  
PROTON RAHMAN ◽  
MICHAEL O. WOODS
Keyword(s):  
Rheumatoid Arthritis ◽  
Association Analysis ◽  
Lupus Erythematosus ◽  
Copy Number ◽  
Association Studies ◽  
Copy Number Variations ◽  
Transcription Activator ◽  
Variable Regions ◽  
Genome Wide ◽  
A Genome

Objective.Rheumatoid arthritis (RA) is a complex autoimmune rheumatic disease that is strongly influenced by genetic factors. Numerous genes are convincingly associated with RA, including genes in tumor necrosis factor signaling (TNF) and the nuclear factor-κB pathway. To date, except for genes within the HLA region, no data exist regarding potential copy number variations (CNV) involving RA-associated genes. We set out to identify genes affected by CNV that are associated with RA at a genome-wide level.Methods.Data from the Wellcome Trust Case Control Consortium (WTCCC) were used in our analyses. The initial WTCCC cohort genotyped 3004 controls and 1999 RA cases using the GeneChip 500k Mapping Array Set. We performed a comparative intensity analysis using the PennCNV algorithm, which uses a hidden Markov model to detect CNV. A total of 2271 controls and 1572 RA samples passed quality control criteria and were included for association analysis. Association analysis was performed in 2 phases: (1) to identify CNV that are < 1 Mb with a population frequency < 5%; and (2) to identify large CNV that are > 1 Mb. Fishers’ exact test was performed to quantify significance of the CNV.Results.We observed that the genome-wide CNV burden is 2-fold higher in patients with RA compared with controls. We identified 11 rare copy number variable regions with < 5% frequency that had an association with RA that reached a p < 1 × 10−4. These include TNFAIP3 and TNIP1, which has been implicated in association studies for RA, systemic lupus erythematosus, and psoriasis. We identified CNV involving IRF1, which functions as a transcription activator of genes induced by interferons; ALOX5AP and LCP2, involved in inflammatory mediation; B2M, an MHC-class I associated gene; and PRKCH, a gene involved in T cell signaling pathways. A 57 kb deletion with 1% frequency in RA cases at 7p21.3 was also observed. Six of these loci overlap with CNV catalogued in the Database of Genomic Variants.Conclusion.This is the first study to identify non-HLA RA-associated CNV using genome-wide analyses. Validation and functional significance of these deletions/duplications in RA and other autoimmune diseases need to be further investigated.

scholarly journals Automated design of paralogue ratio test assays for the accurate and rapid typing of copy number variation

2013 ◽  
Vol 29 (16) ◽  
pp. 1997-2003 ◽  
Author(s):  
Colin D. Veal ◽  
Hang Xu ◽  
Katherine Reekie ◽  
Robert Free ◽  
Robert J. Hardwick ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Automated Design ◽  
Ratio Test ◽  
Number Variation ◽  
Paralogue Ratio Test

Genotyping of common SIRPB1 copy number variant using Paralogue Ratio Test coupled to MALDI-MS quantification

2015 ◽  
Vol 29 (6) ◽  
pp. 517-521 ◽  
Author(s):  
Jose Luis Royo ◽  
Mariona Pascual-Pons ◽  
Arantxa Lupiañez ◽  
Isabel Sanchez-López ◽  
Joan Fibla
Keyword(s):  
Copy Number ◽  
Copy Number Variant ◽  
Maldi Ms ◽  
Ratio Test ◽  
Paralogue Ratio Test

Relationship of HLA-DRB1 Alleles and Rheumatoid Arthritis in West South of Iran

2017 ◽  
Vol 9 (03) ◽  
Author(s):  
Karim Mowla ◽  
Elham Rajaee M. D. ◽  
Mehrdad Dargahi-MalAmir M. D. ◽  
Neda Yousefinezhad ◽  
Maryam Jamali Hondori
Keyword(s):  
Rheumatoid Arthritis ◽  
Environmental Factors ◽  
Rheumatoid Factor ◽  
Dna Extraction ◽  
Wrist Joint ◽  
Blood Sampling ◽  
Healthy Controls ◽  
Relationship Of ◽  
Synovial Pannus

Background: Rheumatoid arthritis is a systemic multifactor disease that presented with symmetrical polyarthritis more preferably in small wrist joint and ankle. Synovial pannus cause destruction and deformities in joints. The main reason of this disease in unknown, but past researchesshowed that genetically factor play important role beside environmental factors in susceptibility to this entity. Method:100 patients with rheumatoid arthritis diagnosed upon ACR 2010 criteria enrolled study. 92 healthy patents also enrolled DNA studying. of both group was extracted through DNA extraction kits by blood sampling. HLA-DRB1 typing was done by PCR-SSP method. Results: There were no significant differences in HLADRB1 *04, HLADRB1*08 and HLADRB1*11 alleles presentation between patients and healthy controls. Only there were statically significant correlation between HLA-DRB1*08 and Rheumatoid factor positive patents. (P = 0.025).

scholarly journals Prevalence and risk factors for bone loss in rheumatoid arthritis patients from South China: modeled by three methods

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhuoran Hu ◽  
Lei Zhang ◽  
Zhiming Lin ◽  
Changlin Zhao ◽  
Shuiming Xu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Lumbar Spine ◽  
Bone Loss ◽  
South China ◽  
Serum Vitamin ◽  
Tumor Necrosis Factor Inhibitor ◽  
Healthy Controls ◽  
Mineral Density ◽  
Serum Vitamin D

Abstract Background To explore the prevalence of bone loss among patients with rheumatoid arthritis (RA) and healthy controls (HC) and further explored the risk factors for osteopenia and osteoporosis of RA patients. Methods A cross-sectional survey was undertaken in four hospitals in different districts in South China to reveal the prevalence of bone loss in patients. Case records, laboratory tests, and bone mineral density (BMD) results of patients were collected. Traditional multivariable logistic regression analysis and two machine learning methods, including least absolute shrinkage selection operator (LASSO) and random forest (RF) were for exploring the risk factors for osteopenia or osteoporosis in RA patients. Results Four hundred five patients with RA and 198 HC were included. RA patients had lower BMD in almost BMD measurement sites than healthy controls; the decline of lumbar spine BMD was earlier than HC. RA patients were more likely to comorbid with osteopenia and osteoporosis (p for trend < 0.001) in the lumbar spine than HC. Higher serum 25-hydroxyvitamin D3 level and using tumor necrosis factor inhibitor in the last year were protective factors; aging, lower body mass index, and increased serum uric acid might be risk factors for bone loss. Conclusions RA patients were more prone and earlier to have bone loss than HC. More attention should be paid to measuring BMD in RA patients aging with lower BMI or hyperuricemia. Besides, serum vitamin D and all three measurement sites are recommended to check routinely. TNFi usage in the last year might benefit bone mass.

scholarly journals CO0005 C-C CHEMOKINE RECEPTOR TYPE 5 AND ITS LIGANDS CCL4, 8 AND 11 CAN LINK COVID-19, RHEUMATOID ARTHRITIS AND HYDROXYCHLOROQUINE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 213.3-214
Author(s):  
M. Y. Hachim ◽  
S. Hannawi
Keyword(s):  
Rheumatoid Arthritis ◽  
Mechanism Of Action ◽  
Immune Cells ◽  
Health Concern ◽  
Healthy Controls ◽  
Global Public Health ◽  
Ccr5 Expression ◽  
Disease Modifying Drugs ◽  
Link Type ◽  
Disease Modifying

Background:Coronavirus disease (COVID-19) caused by SARS-COV2 represents an unprecedented global public health concern with a particular burden on patients with chronic diseases and those on immune-modulating drugs. It is especially worrisome to patients with rheumatoid arthritis (RA) who are on immune suppression regimens[1]. On the other side, many reports showed and recommended the use of some Disease-Modifying Drugs commonly used to treat rheumatic diseases like hydroxychloroquine. However, the general understanding of COVID-19 characteristics in this population and the mechanism of action of these drugs in COVID-19 is still unknown[2].Objectives:Explore publicly available transcriptomic dataset of patients infected with SARS-COV2 compared to uninfected to identify differentially expressed genes (DEGs) related to the immune system that might be pathogenic in RA synovium. Then explore the effect of Disease-Modifying Drugs on their local expression that might give hints about their possible mechanism of action.Methods:RNAseq dataset (GSE147507) were retrieved using the Gene Expression Omnibus (GEO) and used to identify DEGs between infected and uninfected lung samples using BioJupies tools [3]. The DEGs were explored for common pathways using Metascape online tool (http://metascape.org) [10], as shown in figure (1). The chemokines genes were filtered out, and their common receptor (CR) was identified. The immune cells that express a higher level of the identified receptor were explored using DICE project tool (https://dice-database.org/). The expression of CR was searched in a microarray dataset (GSE77298) of synovial biopsies of RA and healthy controls. RNAseq dataset (GSE97165) of synovial biopsies taken from 19 early RA patients at baseline and after six months of Triple Disease-Modifying Anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine, and hydroxychloroquine) treatment.Results:84 DEGs were identified between uninfected and COVID-19 infected lung samples. These DEGs were enriched in pathways specific to (response to the virus, response to interferon, leukocyte activation, and chemotaxis). Interestingly, SARS-COV-2 infected lungs express more CCL4, CCL8, and CCL11; the three ligands shared the same receptor, which is CCR5. Top immune cells that express CCR5 were CD4 T memory T reg cells, Th17, Th1, and monocytes. CCR5 was significantly upregulated in RA compared to healthy controls synovium (p=0.04) and was dramatically downregulated after six months of tDMARD treatment (p=0.004), as shown in figure (2).Conclusion:Using publicly available transcriptomic datasets properly highlighted the possible beneficiary effect of DMARDs in patients with COVID-19, which can block CCR5 rich immune cells recruitment.References:[1]Favalli, E.G., et al.,COVID-19 infection and rheumatoid arthritis: Faraway, so close!Autoimmun Rev, 2020. 19(5): p. 102523.[2]Gianfrancesco, M.A., et al.,Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries.The Lancet Rheumatology, 2020. 2(5): p. e250-e253.[3]Torre, D., A. Lachmann, and A. Ma’ayan,BioJupies: Automated Generation of Interactive Notebooks for RNA-Seq Data Analysis in the Cloud.Cell Systems, 2018. 7(5): p. 556-561.e3.Figure 1.Flowchart of transcriptomic analysisFigure 2.(A) Top immune cells that express CCR5 (B) CCR5 expression in synovial biopsies of RA and control (C) CCR5 expression at baseline and after 6 months of tDMARD treatment.Disclosure of Interests:None declared

scholarly journals POS0583 ENGINEERED GLOVE TO EVALUATE THE SPEED OF THE HANDS’ MOVEMENTS IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 524.3-525
Author(s):  
M. Patanè ◽  
L. Carmisciano ◽  
E. Hysa ◽  
E. Gotelli ◽  
A. Signori ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Health Assessment ◽  
Continuous Variable ◽  
Test System ◽  
Movement Speed ◽  
Healthy Controls ◽  
Activity Class ◽  
Patient Reported ◽  
Opposition Movements

Background:Rheumatoid arthritis (RA) is a long-term, progressive, and disabling autoimmune disease1. The disease activity can be quantified by the Disease Activity Score 28-joint count – C reactive protein (DAS28crp)2; the evaluation of disability function (DF) is actually mainly performed only by subjective Patient Reported Outcomes (PROs) like Health Assessment Questionnaire (HAQ)3; to investigate the functional aspects of RA hands it is usually used the grip strength (GS)4. However, in the scientific literature no tool, which objectively evaluates movement speed, has been reported. The Hand Test System (HTS, ETT) is an engineered glove (RAGLOVE), nowadays applied for neuroscience studies to evaluate hand motility5Objectives:To objectively evaluate the RA hand’s speed of the fine movements, through the HTS and to compared with a group of age and sex matched healthy controls. To verify the correspondence with the HAQ, DAS28, GS.Methods:55 consecutives RA patients (pts) (6 males, age 61 ± 16 years, mean duration of disease 12 ± 8 years), classified according to 2010 ACR/EULAR criteria6, and 50 matched healthy controls (HCs) were enrolled. After consent, all participants undergone HTS test that recognizes the touches between the finger tips during the opposition movements of the hands in standard sequences of movements, after dressed the glove. A multiple finger evaluation (MFE) and a single finger evaluation (SFE) were performed using a dedicated software that provided the physician the following quantitative parameters: Touch Duration (TD), Inter Tapping Interval (ITI) and Movement Rate (MR). Average time for hand 2 minutes. RA pts compiled the HAQ, performed the GS and a DAS28cpr was performed.The student’s t-test was used to compare the glove’s parameters between the groups whereas the analysis of variance (ANOVA) was utilized to verify potential differences between the populations. In order to evaluate the single correlations, the r and p values of Pearson were employed.Results:For MFE, glove parameters TD and ITI were significantly higher in RA pts than HCs, whereas; MR was significantly lower in RA pts compared to HCs (all p <0.001).For SFE non-affected fingers (not swollen and not tender) of RA pts performed better than a clinically affected fingers, but in any case significantly worse than average HCs fingers (p < 0.001).There is a statistically significant correlation between the GS and MR (r= 0.39 p=0.003) and TD (r=-0.33 p=0.015).TD, ITI e MR of RA pts showed a significant correlation with the total score of the HAQ (r = 0.56, r = 0.39, r = -0.56, all p < 0.001;). DAS28, considered as a continuous variable, proved to be significantly correlated with the TD (r = 0.36, p = 0.009). When the RA patients were grouped according to the disease activity by DAS28cpr7, there was an increase of one third of the TD’s logarithm for each increase in the activity class (linear regression with ordinal predictors, beta = 0.33; 95%CI 0.03, 0.63,p < 0.0297). Finally, even RA pts in remission showed a TD significantly higher compared with HCs (p= 0.034).Conclusion:The RAGLOVE is shown as a new safe and fast tool to evaluate a new objective parameter in the hand’s functionality: the speed of finger movements. In RA pts, an inversely proportional correlation emerges between the speed of movement and disease activity.The significant correlation found with HAQ, highlights the loss of motility of the hands as one of the main determinant of disability. The RAGLOVE is now tested in RA patients undergoing treatment.References:[1]Hakkinen et al Ann Rheum Dis. 2005;[2]Van Der Heijde et al J of Rheum. 1993;[3]Fries et al Arthritis Rheum. 1980;[4]Mathiowetz et al J Hand Surg Am. 1984;[5]Carmisciano et al Eur J Neurol. 2020;[6]Aletaha et al. Ann Rheum Dis. 2010;[7]Aletaha et al Arthritis Rheum 2005.Disclosure of Interests:None declared

scholarly journals SAT0077 CARDIOVASCULAR RISK ASSESSMENT WITH CAROTID ULTRASONOGRAPHY IN ADDITION TO THE TRADITIONAL CARDIOVASCULAR RISK FACTORS IN RHEUMATOID ARTHRITIS PATIENTS: A CASE CONTROL STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 973-973
Author(s):  
R. Gonzalez Mazario ◽  
J. J. Fragio-Gil ◽  
P. Martinez Calabuig ◽  
E. Grau García ◽  
M. De la Rubia Navarro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Disease Duration ◽  
Case Control Study ◽  
Case Control ◽  
Healthy Controls ◽  
Carotid Ultrasonography ◽  
Control Study

Background:Cardiovascular disease (CV) is the most frequent cause of death in rheumatoid arthritis (RA) patients. It is well known that RA acts as an independent cardiovascular risk factor.Objectives:To assess the CV risk in RA patients using carotid ultrasonography (US) additionally to the traditional CV risk factors.Methods:A prospective transversal case control study was performed, including adult RA patients who fulfilled ACR/EULAR 2010 criteria and healthy controls matched according to CV risk factors. Population over 75 years old, patients with established CV disease and/or chronic kidney failure (from III stage) were excluded. The US evaluator was blinded to the case/control condition and evaluated the presence of plaques and the intima-media thickness. Statistical analysis was performed with R (3.6.1 version) and included a multivariate variance analysis (MANOVA) and a negative binomial regression adjusted by confounding factors (age, sex and CV risk factors).Results:A total of 200 cases and 111 healthy controls were included in the study. Demographical, clinical and US data are exposed in table 1. Not any difference was detected in terms of CV risk factors between the cases and controls. In both groups a relationship between age, BMI and high blood pressure was detected (p<0.001).Table 1.Table 2.RA basal characteristicsDisease duration (years)16,98 (11,38)Erosions (X-Ray of hands/feet)163 (81,5%)Seropositive (RF/anti-CCP)146 (73%)Extra-articular symptoms44 (22%)Intersticial difusse lung disease10 (5%)Rheumatoid nodules14 (7%)Prednisone use103 (51,5%)Median dose of Prednisone last year (mg)2,34 (2,84)sDMARDsMethotrexate104 (52%)Leflunomide29 (14,5%)Hydroxycloroquine9 (4,5%)bDMARDs89 (44,5%) TNFi41 (20,5%) Abatacept15 (7,5%) IL6i22 (11%) RTX11 (5,5%)JAKi26 (13%) Baricitinib11 (5,5%) Tofacitinib15 (7,5%)DAS 28-ESR3,1 (2,3, 3,9)SDAI7,85 (4,04, 13,41)HAQ0,88 (0,22, 1,5)RF (U/mL)51 (15, 164,25)Anti-CCP (U/mL)173 (22, 340)Patients showed higher intima-media (both right and left) thickness compared to controls (p<0.006). Moreover it was also related to the disease duration and DAS28 score (p<0.001). A higher plaque account was noted in cases(p<0.004) and it was also related to the disease duration (p<0.001).Conclusion:RA implies a higher CV risk. Traditional CV risk factors explains only partially the global risk. These findings support that RA acts as an independent cardiovascular risk factor.Disclosure of Interests:None declared

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