scholarly journals Linkage and Association Studies of Joint Morbidity from Rheumatoid Arthritis

2009 ◽  
Vol 37 (2) ◽  
pp. 291-295 ◽  
Author(s):  
JIN-YOUNG MIN ◽  
KYOUNG-BOK MIN ◽  
JOOHON SUNG ◽  
SUNG-IL CHO
Keyword(s):  
Rheumatoid Arthritis ◽  
Association Studies ◽  
Clinical Signs ◽  
Joint Damage ◽  
Genetic Variations ◽  
Nucleotide Polymorphisms ◽  
Sibling Pairs ◽  
Rf Values ◽  
Family Based ◽  
The Relationship

Objective. To investigate the relationship between genetic variations of rheumatoid arthritis (RA) susceptibility in terms of joint morbidity.Methods. We used data from Genetic Analysis Workshop 15. The Illumina linkage panel IV included 5858 single-nucleotide polymorphisms (SNP), with 5744 SNP passing quality control filters. The phenotypic variables analyzed were the level of rheumatoid factor (RF) and score on the Joint Alignment and Motion (JAM) scale. We modified the scale, dividing by RF values relevant to disease severity. Linkage analysis for affected sibling pairs was done using the MERLIN program, and family-based association tests were carried out using PLINK and FBAT software.Results. We found a high peak (LOD = 3.29; NPL Z = 4.07) near the HLA-DRB1 region on chromosome 6. The linkage at 6p24 at rs1410766 [LOD = 2.66; nonparametric linkage (NPL) Z = 3.23] was statistically significant. Two other regions also showed possible linkage peaks: chromosome 7q30 at rs322812 (LOD = 2.47; NPL Z = 3.39) and chromosome 15p34 at rs347117 (LOD = 1.95; NPL Z = 2.80). For the family-based association study, 7 SNP related to clinical RA severity were detected.Conclusion. Genetic variations may lead to an enhanced risk of joint damage and increased levels of RF. Further studies are needed to elucidate the roles of other genes involved in RA and to explore whether the clinical signs of RA are associated with particular genetic variations.

Association ofEMCNwith Susceptibility to Rheumatoid Arthritis in a Japanese Population

2010 ◽  
Vol 38 (2) ◽  
pp. 221-228 ◽  
Author(s):  
KAZUMASA NISHIMOTO ◽  
KATSUNORI IKARI ◽  
HIROTAKA KANEKO ◽  
SO TSUKAHARA ◽  
YUTA KOCHI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Association Studies ◽  
Functional Study ◽  
Positive Staining ◽  
Nucleotide Polymorphisms ◽  
Data Set ◽  
Nuclear Factors ◽  
Validation Set ◽  
Synovial Tissues ◽  
Stratified Analysis

Objective.Endomucin, an endothelial-specific sialomucin, is thought to facilitate “lymphocyte homing” to synovial tissues, resulting in the major histopathologies of rheumatoid arthritis (RA). We examined the association between RA susceptibility and the gene coding endomucin,EMCN.Methods.Association studies were conducted with 2 DNA sample sets (initial set of 1504 patients, 752 controls; and validation set, 1113 patients, 940 controls) using 6 tag single-nucleotide polymorphisms (SNP) from the Japanese HapMap database. Immunohistochemistry for the expression of endomucin was conducted with synovial tissues from 4 patients with RA during total knee arthroplasty. Electromobility shift assays were performed for the functional study of identified polymorphisms.Results.Within the initial sample set, the strongest evidence of an association with RA susceptibility was SNP rs3775369 (OR 1.20, p = 0.0075). While the subsequent replication study did not initially confirm the observed significant association (OR 1.13, p = 0.062), an in-depth stratified analysis revealed significant association in patients testing positive to anti-cyclic citrullinated peptide (anti-CCP) antibody in the replication data set (OR 1.15, p = 0.044). Investigating 2 sample sets, significant associations were detected in overall and stratified samples with anti-CCP antibody status (OR 1.17, p = 0.0015). Positive staining for endomucin was detected in all patients. The allele associated with RA susceptibility had a higher binding affinity for HEK298-derived nuclear factors compared to the nonsusceptible allelic variant of rs3775369.Conclusion.A significant association betweenEMCNand RA susceptibility was detected in our Japanese study population. TheEMCNallele conferring RA susceptibility may also contribute to the pathogenesis of RA.

scholarly journals Factors associated with rs1801394 of the methionine synthase reductase gene polymorphism in patients with rheumatoid arthritis

2021 ◽  
Vol 15 (3) ◽  
pp. 15-19
Author(s):  
M. Yu. Krylov ◽  
G. I. Gridneva ◽  
Yu. V. Muravyev
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Characteristics ◽  
Methionine Synthase ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination ◽  
Methionine Synthase Reductase ◽  
Reductase Gene ◽  
Group 2 ◽  
The Relationship ◽  
Group 1

Clinical response to methotrexate (MT) therapy in rheumatoid arthritis (RA) can be predicted on the basis of some single nucleotide polymorphisms (SNPs) of genes, involved in folate metabolism. One of these SNPs is the rs1801394 (A66G) polymorphism of the methionine synthase reductase gene (MTRR). We investigated the association of this polymorphism with the clinical characteristics of RA patients after 6 months of MT therapy. Studies of the relationship between the response to MT therapy and the rs1801394 polymorphism have not been carried out in Russia previously.Objective: to study the possible association of the rs1801394 polymorphism with the clinical characteristics of patients with RA after 6 months of MT therapy.Patients and methods. The study included 60 patients with RA who met the ACR / EULAR criteria (2010) and received≥20 mg MT per week continuously. Based on the EULAR criteria, patients were divided into two groups: group 1 (n=30) with a good (DAS28>1.2) and group 2 (n=30) with an unsatisfactory (DAS28 <1.2) response to MT therapy. Genotyping of the rs1801394 polymorphism was performed by allelic discrimination using real-time polymerase chain reaction.Results and discussion. The frequency distribution of the A66G polymorphism genotypes in both groups was similar, however, in the 2nd group with an unsatisfactory response, there was a tendency towards a higher frequency of the mutant GG genotype (p=0.067). An association of the A66G polymorphism with gender and disease duration was found. In group 1, the AG genotype was more often detected in men than in women (p=0.017). In group 2, the AG genotype was also more common in men (p=0.075). In addition, in this group, carriers of the G allele (genotypes AG and GG) had a longer duration of the disease than carriers of the AA genotype (p=0.003 and p=0.005, respectively).Conclusion. In the present study, the relationship of the studied polymorphism rs1801394 of the MTRR gene with gender and duration of RA disease was established.

SAT0119 The relationship between inflammation and joint damage in rheumatoid arthritis is dependent on anti-CCP status

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 510.2-511
Author(s):  
Y. De Punder ◽  
J. Hendrikx ◽  
E. Valls Pascual ◽  
P. van Riel ◽  
J. Fransen
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Damage ◽  
The Relationship

Abstract 18134: Phenome-wide Study of Electronic Medical Record Data Reveals Novel Association of Natriuretic Peptide A Genetic Variant With Rheumatoid Arthritis

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Naveen Pereira ◽  
Gregory Jenkins ◽  
Ifthikar Kullo ◽  
Suzette Bielinski ◽  
John Burnett ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Genetic Variation ◽  
Medical Record ◽  
Electronic Medical Record ◽  
Natriuretic Peptide ◽  
Genetic Variants ◽  
Association Studies ◽  
Disease Phenotypes ◽  
Novel Association ◽  
The Relationship

Introduction: Phenome-wide association studies (PheWAS) using electronic medical record (EMR)-linked biobanks have been used not only to identify and replicate known associations of genetic variants with disease phenotypes but have also resulted in the discovery of potentially novel genotype-phenotype relationships. The natriuretic peptide (NP) system plays an important role in a broad range of disease processes including cardiovascular and inflammatory diseases. We hypothesized that performing a PheWAS using previously known functional genetic variants of the NP system may result in novel disease associations that could provide mechanistic insights in an unbiased manner. Methods: We scanned for associations between 9 single-nucleotide polymorphisms (SNPs) in the NP system and 27 EMR-derived chronic disease phenotypes in 3,025 individuals participating in a case-control study of peripheral arterial disease. The EMR phenotypes were identified using two or more ICD-9-CM diagnosis codes based on the AHRQ Clinical Classifications Software (CCS). The relationship of SNPs and phenotypes were modeled using logistic regression adjusting for gender. Results: We identified rs5065, a SNP located in the stop codon of exon 3 of the NPPA gene, to be the strongest associated SNP with rheumatoid arthritis (RA) (OR=0.78, p=0.0008, q-value=0.11). The SNP leads to the extension of atrial natriuretic peptide (ANP) by 2 additional arginines at the C terminus. Cardiovascular disease is known to be the leading cause of death in patients with RA and ANP plays an important immunomodulatory role by inhibiting inducible nitric oxide synthase, reducing TNF-α production and attenuating prostaglandin E2 production in macrophages. Circulating NPs have been used to screen for occult cardiac disease and are associated with mortality in RA. This study demonstrates for the first time the importance of the relationship between genetic variation in the NP system and RA. Conclusions: PheWAS was successfully used as a tool to identify a novel association of functional genetic variation in the NPPA gene with RA. The observation is hypothesis generating and further replication studies are required to determine the role of rs5065 in cardiovascular outcomes of RA.

scholarly journals The Relationship Between Synovial Pathobiology and Magnetic Resonance Imaging Abnormalities in Rheumatoid Arthritis: A Systematic Review

2017 ◽  
Vol 44 (9) ◽  
pp. 1311-1324 ◽  
Author(s):  
Frances Humby ◽  
Arti Mahto ◽  
Muaaze Ahmed ◽  
Andrew Barr ◽  
Stephen Kelly ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Magnetic Resonance Imaging ◽  
Systematic Review ◽  
Bone Marrow ◽  
Magnetic Resonance ◽  
Bone Erosion ◽  
Critical Role ◽  
Joint Damage ◽  
Resonance Imaging ◽  
The Relationship

Objective.Magnetic resonance imaging (MRI) has been increasingly recognized as a critical tool for the assessment of patients with rheumatoid arthritis (RA) and is able to reliably identify synovitis, bone marrow edema, bone erosion, and joint space narrowing (JSN)/cartilage loss. Understanding the exact relationship between each MRI feature and local synovial pathobiology is critical to dissect disease pathogenesis as well as develop future predictive models.Methods.A systematic review was performed of the current published literature examining the relationship between MRI abnormalities and synovial pathobiology in patients with RA.Results.Eighteen studies were identified; most focused on validation of MRI as a tool to detect and quantify synovitis, with a significant relationship demonstrated. Additionally, from the limited data available, a critical role seems likely for synovial pathways, at least in driving joint damage. However, there was a lack of data examining the relationship between synovial pathobiology and bone marrow abnormalities and JSN.Conclusion.Although understanding the interrelationship of these disease biomarkers offers the potential to enhance the predictive validity of modern imaging with concomitant synovial pathobiological analysis, further studies integrating MRI with synovial tissue analysis in well-controlled cohorts at distinct disease stages before and after therapeutic intervention are required to achieve this.

Epistatic Interaction between Fibrinogen alpha and gamma Genes and Factor V Leiden in Children with Venous Thrombosis: Results from a Family-Based Association Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1640-1640
Author(s):  
Ulrike Nowak-Gottl ◽  
Hartmut Weiler ◽  
Tanja Seehafer ◽  
Sabine Thedieck ◽  
Monika Stoll
Keyword(s):  
Genetic Variation ◽  
Epistatic Interaction ◽  
Association Studies ◽  
Factor V Leiden ◽  
Complex Nature ◽  
Factor V ◽  
Nucleotide Polymorphisms ◽  
Permutation Testing ◽  
Factor V Leiden Mutation ◽  
Family Based

Abstract Background: Fibrinogen, the precursor of fibrin, is an essential component of the hemostatic system. A previous large case-control study showed that genetic variation in the fibrinogen gamma gene (FGG) increased the risk for VT in adults. Here we investigated the association of haplotypes comprising the fibrinogen alpha (FGA) and gamma (FGG) genes, carriership of the Factor V Leiden mutation and risk for VT in a large family-based study sample for pediatric VT. Methods: We genotyped 188 pediatric VT families for seven single nucleotide polymorphisms (SNPs) (rs6050, rs2070016, rs2070014 and rs2070011, rs1049636, rs2066861, rs2066860) as well as the G1691A Factor V Leiden (FV) polymorphism. Association was assessed using the Transmission Disequilibrium Test (TDT) and corrected for multiple testing using permutation testing as implemented in HAPLOVIEW. Interaction between FV and FGA and FGG, respectively, was assessed by TDT in families stratified for presence or absence of the FV mutation in the affected child. Results: rs6050, rs2070016, rs2070014 and rs2070011 located in the FGA gene are in tight linkage disequilibrium (LD) and define 5 common haplotypes (HT) and are linked with the neighboring FGG gene (q= 0.91). rs1049636, rs2066861, rs2066860 located in FGG are in tight LD and define 4 HTs. HTs in both, FGA and FGG are significantly overtransmitted from parents to affected offspring (FGA: HT1 (AACT), HT frequency 0.32, T:U 62: 32, p=0.0025; FGG: HT2 (ATC), HT frequency 0.32, T:U 60:32, p=0.0035). When stratifying for FV status, it became apparent that the association between FGA and FGG and VT was more pronounced in FV-negative families (FGA, HT1, T:U 55:24, p=0.0006; FGG, HT2, T:U 55:24, p=0.0005), while absent in FV-positive families. Conclusion: Our results indicate that genetic variation in FGA and FGG are risk factors for VT in children, and further that an epistatic interaction between FGA/FGG and FV Leiden influences the risk of FGG and FGA on pediatric VT. Our study highlights the complex nature of VT and the necessity to evaluate gene-gene interactions in association studies of complex, polygenic diseases.

scholarly journals Genetic Variants Shaping Inter-individual Differences in Response to Dietary Intakes—A Narrative Review of the Case of Vitamins

2020 ◽  
Vol 7 ◽  
Author(s):  
Aikaterini Niforou ◽  
Valentini Konstantinidou ◽  
Androniki Naska
Keyword(s):  
Vitamin D ◽  
Vitamin C ◽  
Genetic Variants ◽  
Current Knowledge ◽  
Association Studies ◽  
Genetic Variations ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Dietary Intakes ◽  
Genes Encoding

Recent advances in the field of nutrigenetics have provided evidence on how genetic variations can impact the individuals' response to dietary intakes. An objective and reliable assessment of dietary exposures should rely on combinations of methodologies including frequency questionnaires, short-term recalls or records, together with biological samples to evaluate markers of intake or status and to identify genetic susceptibilities. In an attempt to present current knowledge on how genetic fingerprints contribute to an individual's nutritional status, we present a review of current literature describing associations between genetic variants and levels of well-established biomarkers of vitamin status in free-living and generally healthy individuals. Based on the outcomes of candidate gene, genome-wide-association studies and meta-analyses thereof, we have identified several single nucleotide polymorphisms (SNPs) involved in the vitamins' metabolic pathways. Polymorphisms in genes encoding proteins involved in vitamin metabolism and transport are reported to have an impact on vitamin D status; while genetic variants of vitamin D receptor were most frequently associated with health outcomes. Genetic variations that can influence vitamin E status include SNPs involved in its uptake and transport, such as in SCAR-B1 gene, and in lipoprotein metabolism. Variants of the genes encoding the sodium-dependent vitamin C transport proteins are greatly associated with the body's status on vitamin C. Regarding the vitamins of the B-complex, special reference is made to the widely studied variant in the MTHFR gene. Methodological attributes of genetic studies that may limit the comparability and interpretability of the findings are also discussed. Our understanding of how genes affect our responses to nutritional triggers will enhance our capacity to evaluate dietary exposure and design personalized nutrition programs to sustain health and prevent disease.

The relationship between joint damage and functional disability in rheumatoid arthritis: a systematic review

2011 ◽  
Vol 71 (6) ◽  
pp. 836-844 ◽  
Author(s):  
Claire Bombardier ◽  
Marco Barbieri ◽  
Anju Parthan ◽  
Debra J Zack ◽  
Valery Walker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Functional Disability ◽  
Joint Damage ◽  
The Relationship

scholarly journals Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis

2009 ◽  
Vol 69 (3) ◽  
pp. 567-570 ◽  
Author(s):  
Hans Ulrich Scherer ◽  
Michael P M van der Linden ◽  
Fina A S Kurreeman ◽  
Gerrie Stoeken-Rijsbergen ◽  
Saskia le Cessie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Severe Disease ◽  
Joint Destruction ◽  
Joint Damage ◽  
Negative Regulator ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Factor Α

BackgroundTwo novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumour necrosis factor α-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NF-κB and is involved in inhibiting TNF-receptor-mediated signalling effects. Interestingly, the initial associations were detected in patients with longstanding RA. However, no association was found for rs10499194 in a Swedish cohort with early arthritis. This might be caused by over-representation of patients with severe disease in cohorts with longstanding RA.ObjectiveTo analyse the effect of the 6q23 region on the rate of joint destruction.MethodsFive single nucleotide polymorphisms in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated with progression of radiographic joint damage for a follow-up time of 5 years.ResultsTwo polymorphisms (rs675520 and rs9376293) were associated with severity of radiographic joint damage in patients positive for anti-citrullinated protein/peptide antibodies (ACPA). Importantly, the effects were present after correction for confounding factors such as secular trends in treatment.ConclusionsThese data associate the 6q23 region with the rate of joint destruction in ACPA+ RA.

scholarly journals AB0864-HPR INFLUENCE OF THE TYPE OF PAIN SYNDROME ON THE SEVERITY OF ANXIETY-DEPRESSIVE DISORDERS IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1455.2-1456
Author(s):  
E. Egorova ◽  
N. Nikitina ◽  
A. Rebrov
Keyword(s):  
Rheumatoid Arthritis ◽  
Severe Pain ◽  
Depressive Disorders ◽  
Functional Limitations ◽  
Joint Damage ◽  
Statistical Processing ◽  
Pain Syndrome ◽  
Anxiety And Depression ◽  
Moderate Pain ◽  
The Relationship

Background:Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint damage and deformation. Pain syndrome, along with functional limitations, causes the emergence of anxiety-depressive disorders. The patient’s psycho-emotional characteristics affect the patient’s quality of life and the effectiveness of the therapy. The aim: to assess the severity of anxiety and depression in women with rheumatoid arthritis, depending on the type of the pain syndrome.Objectives:The study included 163 women with RA according to the EULAR / ACR 2010 criteria (age 53,9 ± 10,15 years, RA duration - 10 [4; 14] years, DAS28 – 5,03 [4,35; 5,8]).Methods:We used the Hospital Depression and Anxiety Scale (HADS) questionnaire: 0-7 points were assessed as the absence of significant symptoms of anxiety and depression, 8-10 points - subclinically expressed anxiety and depression, more than 11 points - clinically expressed anxiety and depression. The severity of pain was determined by the VAS: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), severe pain (75-100 mm). Assessment of the type of pain (identification of the neuropathic component of pain) was carried out using the DN4 questionnaire: a sum of 4 or more points indicated the presence of a neuropathic component of pain (NCP). Statistical processing was performed using the STATISTICA 10,0 program.Results:The frequency of occurrence of anxiety-depressive disorders in RA patients was determined: clinically pronounced anxiety was detected in 35 (21,4%) patients, depression - in 34 (20,9%); subclinically expressed anxiety - in 42 (25,8%), depression - in 44 (27%) patients; absence of reliably pronounced symptoms of anxiety - in 86 (52,8%) patients, depression - in 85 (52,1%) patients.Severe pain according to VAS was noted in 57 (35%) patients, moderate pain - in 75 (46%), in 31 (19%) patients the pain syndrome was mild. In 81 (49,7%) patients a neuropathic component of pain was revealed.The relationship was established between the presence of NCP and the severity of anxiety (r = 0,27, p < 0,05), depression (r = 0,31, p <0,05). The relationship was revealed between the presence of NCP and the severity of pain according to the VAS (r = 0.32, p <0.05).To explain the relationship between the presence of NCP and anxiety-depressive disorders, the patients were divided into two groups depending on the presence of NCP, comparable in age, the main clinical characteristics of RA, and basic therapy. The level of anxiety in women with NCP (9,5 [7; 13]) was significantly higher than in patients without NCP (6.1 [4; 9]) (p = 0.01). The severity of depression in women with NCP was 8,55 [6; 11], in patients without NCP – 5,15 [3; 6] (p = 0.005).Conclusion:Thus, every fifth patient with RA had clinically significance anxiety and depression, subclinical anxiety and depression were found in 26% of RA patients. Most of the patients (81%) had moderate or severe pain, half of the patients had signs of neuropathic pain. The relationship between the severity of anxiety and depression with the intensity of pain and the presence of a neuropathic component was revealed.Disclosure of Interests:None declared

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