scholarly journals Role of European mitochondrial DNA haplogroups in the prevalence of hip osteoarthritis in Galicia, Northern Spain

2009 ◽  
Vol 69 (01) ◽  
pp. 210-213 ◽  
Author(s):  
I Rego ◽  
M Fernández-Moreno ◽  
C Fernández-López ◽  
J J Gómez-Reino ◽  
A González ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mitochondrial Dna ◽  
Multivariate Analysis ◽  
Hip Osteoarthritis ◽  
Spanish Population ◽  
Healthy Controls ◽  
Northern Spain ◽  
Mtdna Haplogroups ◽  
Study Support

Objective:To analyse the mitochondrial DNA (mtDNA) haplogroups of patients with hip osteoarthritis (OA) and those of healthy controls in a Spanish population.Methods:mtDNA haplogroups were assigned to 550 cases of hip OA and 505 clinically asymptomatic controls. Sets of controls with healthy knees and hips (n = 179) and patients with knee and/or hip OA (n = 977) were also analysed in a multivariate analysis after adjusting for sex, age and smoking.Results:Individuals carrying haplogroup J showed a significantly decreased risk of developing hip OA (OR 0.661; 95% CI 0.440 to 0.993; p = 0.045). In addition to haplogroup J, smoking protected against the development of hip OA (OR 0.543; 95% CI 0.311 to 0.946; p = 0.031). However, no relationship was found between rheumatoid arthritis and mtDNA haplogroups.Conclusion:The results of this study support the hypothesis that the mtDNA haplogroups have a role in the complex osteoarthritic process.

miR-216a-5p Suppresses the Proliferation, Invasion and Migration of Fibroblast-Like Synoviocyte in Rheumatoid Arthritis by Targeting Zinc Finger and BTB Domain-Containing Protein 2 (ZBTB2)

2021 ◽  
Vol 11 (5) ◽  
pp. 896-902
Author(s):  
Jinwei Zhao ◽  
Ling Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Zinc Finger ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Healthy Controls ◽  
Invasion And Migration ◽  
Btb Domain ◽  
And Migration

MicroRNAs have been reported to be associated with the initiation and progression of rheumatoid arthritis (RA). miR-216a-5p, one of the miRNAs, is involved in cancer cell proliferation, invasion and migration. However, the role of miR-216a-5p in RA remains to be explored. The expressions of miR-216a-5p and zinc finger and BTB domain-containing protein 2 (ZBTB2) in fibroblast-like synoviocytes (FLS) of RA or healthy controls were detected by qRT-PCR and western blot analysis. Transfection of overexpressed and silenced miR-216a-5p were performed to explore the functional role of miR-216a-5p in RA-FLS. Cell Counting Kit-8 (CCK-8) assay and transwell assay were employed to assess cell proliferation and cell invasion, respectively. Moreover, luciferase reporter assay was executed to verify the combination of miR-216a-5p and ZBTB2. The results showed that miR-216a-5p expression in RA-FLS was downregulated than healthy controls. Overexpres-sion of miR-216a-5p inhibited RA-FLS cell proliferation, invasion and migration, while miR-216a-5p silencing revealed the opposite results. In addition, ZBTB2 was identified to be a direct target of miR-216a-5p in RA-FLS and its expression was higher than that in healthy controls. Rescue experiments revealed that ZBTB2 overexpression reversed the effects of miR-216a-5p on the proliferation, invasion and migration of RA-FLS. These data indicated the suppressive role of miR-216a-5p in RA-FLS via the regulation of ZBTB2, suggesting that miR-216a-5p and ZBTB2 may be the new targets for the treatment of RA.

scholarly journals The Role of Simvastatin in the Therapeutic Approach of Rheumatoid Arthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Lucia Cojocaru ◽  
Andrei Constantin Rusali ◽  
Cristina Şuţa ◽  
Anca Mihaela Rădulescu ◽  
Maria Şuţa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Active Rheumatoid Arthritis ◽  
Therapeutic Potential ◽  
Efficacy And Safety ◽  
Good Safety Profile ◽  
Study Support ◽  
Anti Inflammatory ◽  
Inflammatory Effect

The pleiotropic effects of statins, especially the anti-inflammatory and immunomodulatory ones, indicate that their therapeutic potential might extend beyond cholesterol lowering and cardiovascular disease to other inflammatory disorders such as rheumatoid arthritis. Therefore, we undertook a prospective cohort study to evaluate the efficacy and safety of simvastatin used for inflammation control in patients with rheumatoid arthritis. One hundred patients with active rheumatoid arthritis divided into two equal groups (the study one who received 20 mg/day of simvastatin in addition to prior DMARDs and the control one) were followed up over six months during three study visits. The results of the study support the fact that simvastatin at a dose of 20 mg/day has a low anti-inflammatory effect in patients with rheumatoid arthritis with a good safety profile.

scholarly journals Increased Concentrations of Antibody-Bound Circulatory Cell-Free DNA in Rheumatoid Arthritis

2007 ◽  
Vol 53 (9) ◽  
pp. 1609-1614 ◽  
Author(s):  
Xiao-Yan Zhong ◽  
Ines von Mühlenen ◽  
Ying Li ◽  
Anjeung Kang ◽  
Anurag Kumar Gupta ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Animal Experiments ◽  
Basic Research ◽  
Healthy Controls ◽  
Serum Samples ◽  
Cell Free Dna ◽  
Free Dna ◽  
New Evidence

Abstract Background: Increased concentrations of cell-free DNA have been found in several disorders and have been interpreted as evidence of increased rates of cell death or turnover. Evidence from in vitro and animal experiments suggests that DNA may play a role in the pathogenesis of rheumatoid arthritis (RA). Methods: We measured cell-free DNA in plasma and serum from patients with RA and healthy controls by use of quantitative PCR for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA. We used protein G Sepharose™ bead adsorption of plasma and elution to isolate antibody-bound DNA. Results: In paired plasma and serum samples of 16 healthy controls the median GAPDH copies were 4500 genome equivalents (GE)/mL plasma (range 319–21 000) and in 26 RA patients 17 000 GE/mL plasma (2100–2 375 000, P = 0.0001). In the serum from normal controls the median GAPDH copies were 35 000 GE/mL (1700–239 000) and from RA patients 222 000 GE/mL (21 000–2 375 000, P = 0.004). A median of 81% of the cell-free DNA in RA was associated with antibody compared with 9% in healthy controls (P = 0.001). The concentrations of DNA did not vary with the type of therapy patients received. Conclusions: These results provide new evidence for a role of cell-free DNA-antibody complexes in the etiology of RA, suggest new avenues for basic research, and may prove to be relevant to diagnosis and assessment of therapy.

scholarly journals Dysregulated microRNA expression in rheumatoid arthritis families—a comparison between rheumatoid arthritis patients, their first-degree relatives, and healthy controls

2020 ◽  
Author(s):  
Emma Renman ◽  
Mikael Brink ◽  
Lisbeth Ärlestig ◽  
Solbritt Rantapää-Dahlqvist ◽  
Kristina Lejon
Keyword(s):  
Rheumatoid Arthritis ◽  
Microrna Expression ◽  
Significant Trend ◽  
Healthy Controls ◽  
Altered Expression ◽  
First Degree Relatives ◽  
Key Points ◽  
Polymerase Chain ◽  
And Gender

Abstract Objective Recent studies have demonstrated an altered expression of certain microRNAs in patients with rheumatoid arthritis (RA) as well as their first-degree relatives (FDRs) compared to healthy controls (HCs), suggesting a role of microRNA in the progression of the disease. To corroborate this, a set of well-characterized RA families originating from northern Sweden were analyzed for differential expression of a selected set of microRNAs. Method MicroRNA was isolated from frozen peripheral blood cells obtained from 21 different families and included 26 RA patients, 22 FDRs, and 21 HCs. Expression of the selected microRNAs miR-22-3p, miR-26b-5p, miR-34a-3p, miR-103a-3p, miR-142-3p, miR-146a-5p, miR-155, miR-346, and miR-451a was determined by a two-step quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis including clinical variables was applied. Results Out of the nine selected microRNAs that previously have been linked to RA, we confirmed four after adjusting for age and gender, i.e., miR-22-3p (p = 0.020), miR-26b-5p (p = 0.018), miR-142-3p (p = 0.005), and miR-155 (p = 0.033). Moreover, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs. In addition, analysis of the effect of corticosteroid use showed modulation of miR-103a-3p expression. Conclusions We confirm that microRNAs seem to be involved in the development of RA, and that the expression pattern in FDR is partly overlapping with RA patients. The contribution of single microRNAs in relation to the complex network including all microRNAs and other molecules is still to be revealed. Key Points• Expression levels of miR-22-3p, miR-26b-5p, miR-142-3p, and miR-155 were significantly altered in RA patients compared to those in controls.• In first-degree relatives, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs.

scholarly journals Mitochondrial DNA haplogroups and risk of attention deficit and hyperactivity disorder in European Americans

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiao Chang ◽  
Yichuan Liu ◽  
Frank Mentch ◽  
Joseph Glessner ◽  
Huiqi Qu ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Attention Deficit ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Mtdna Haplogroups ◽  
Hyperactivity Disorder ◽  
European Americans ◽  
Increased Risk ◽  
Control Study

Abstract Although mitochondrial dysfunction has been implicated in the pathophysiology of attention deficit and hyperactivity disorder ADHD, the role of mitochondrial DNA (mtDNA) has not been extensively investigated. To determine whether mtDNA haplogroups influence risk of ADHD, we performed a case-control study comprising 2076 ADHD cases and 5078 healthy controls, all of whom were European decedents recruited from The Children’s Hospital of Philadelphia (CHOP). Associations between eight major European mtDNA Haplogroups and ADHD risk were assessed in three independent European cohorts. Meta-analysis of the three studies indicated that mtDNA haplogroups K (odds ratio = 0.69, P = 2.24 × 10−4, Pcorrected = 1.79 × 10−3) and U (odds ratio = 0.77, P = 8.88 × 10−4, Pcorrected = 7.11 × 10−3) were significantly associated with reduced risk of ADHD. In contrast, haplogroup HHV* (odds ratio = 1.18, P = 2.32 × 10−3, Pcorrected = 0.019) was significantly associated with increased risk of ADHD. Our results provide novel insight into the genetic basis of ADHD, implicating mitochondrial mechanisms in the pathophysiology of this relatively common psychiatric disorder.

scholarly journals Association of Mitochondrial DNA Genomic Variation With Risk of Pick Disease

Neurology ◽  
2021 ◽  
Vol 96 (13) ◽  
pp. e1755-e1760
Author(s):  
Rebecca R. Valentino ◽  
Michael G. Heckman ◽  
Patrick W. Johnson ◽  
Matthew C. Baker ◽  
Alexandra I. Soto-Beasley ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mayo Clinic ◽  
Case Control ◽  
Control Analysis ◽  
Healthy Controls ◽  
Mitochondrial Haplogroups ◽  
Mtdna Haplogroups ◽  
Increased Risk ◽  
Pick Disease ◽  
Mtdna Haplogroup

ObjectiveTo determine whether stable polymorphisms that define mitochondrial haplogroups in mitochondrial DNA (mtDNA) are associated with Pick disease risk, we genotyped 52 pathologically confirmed cases of Pick disease and 910 neurologically healthy controls and performed case-control association analysis.MethodsFifty-two pathologically confirmed cases of Pick disease from Mayo Clinic Florida (n = 38) and the University of Pennsylvania (n = 14) and 910 neurologically healthy controls collected from Mayo Clinic Florida were genotyped for unique mtDNA haplogroup-defining variants. Mitochondrial haplogroups were determined, and in a case-control analysis, associations of mtDNA haplogroups with risk of Pick disease were evaluated with logistic regression models that were adjusted for age and sex.ResultsNo individual mtDNA haplogroups or superhaplogroups were significantly associated with risk of Pick disease after adjustment for multiple testing (p < 0.0021, considered significant). However, nominally significant (p < 0.05) associations toward an increased risk of Pick disease were observed for mtDNA haplogroup W (5.8% cases vs 1.6% controls, odds ratio [OR] 4.78, p = 0.020) and subhaplogroup H4 (5.8% cases vs 1.2% controls, OR 4.82, p = 0.021).ConclusionOur findings indicate that mtDNA variation is not a disease driver but may influence disease susceptibility. Ongoing genetic assessments in larger cohorts of Pick disease are currently underway.

scholarly journals A systematic review of CXCL13 as a biomarker of disease and treatment response in rheumatoid arthritis

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Katie Bechman ◽  
Anthony Dalrymple ◽  
Charles Southey-Bassols ◽  
Andrew P. Cope ◽  
James B. Galloway
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Disease Activity ◽  
Treatment Response ◽  
Janus Kinase ◽  
Response To Treatment ◽  
Healthy Controls ◽  
Treatment Prediction ◽  
Randomised Controlled

Abstract Background The B cell chemoattractant CXCL13 is a promising biomarker in rheumatoid arthritis (RA), with a plausible role in supporting diagnosis, monitoring disease activity and as a prognostic value. It is a key chemokine driving the formation of lymphoid follicles within the inflamed synovium. The objective of this systematic review was to evaluate the role of CXCL13 as a viable biomarker in RA. Methods We conducted a systematic literature review of all published cohort and randomised controlled trials evaluating the role of CXCL13 in RA. The primary outcomes were; i) CXCL13 levels in RA patients compared to healthy controls, ii) the correlation between CXCL13 and markers of disease activity, and iii) the association between CXCL13 and treatment response. Results The search produced 278 articles, of which 31 met the inclusion criteria. Of the 12 studies evaluating CXCL13 expression in early or established RA, all reported higher levels than that seen in healthy controls. Twelve of sixteen studies reported a weakly positive correlation between CXCL13 and markers of disease activity including DAS28 and swollen joint count, with rho values between 0.20–0.67. In 2 studies, CXCL13 levels correlated with ultrasonographic evidence of synovitis. Eighteen studies assessed CXCL13 in response to therapeutic intervention. The majority signified a fall in levels in response to treatment including biologics and Janus kinase (JAK) inhibition. In some, this reduction was only seen in treatment responders. High CXCL13 levels predicted failure to achieve disease remission with csDMARDs. The evidence for treatment prediction with biologics was conflicting. Conclusion Despite evidence to suggest a role in diagnosing RA and in detecting synovitis, the heterogeneity of studies included in this review limit our ability to draw robust conclusions. At present there are inadequate results to justify the routine use of CXCL13 as a biomarker in RA routine clinical practice.

scholarly journals Mitochondrial DNA Haplogroups and Susceptibility to Neuroblastoma

2020 ◽  
Vol 112 (12) ◽  
pp. 1259-1266 ◽  
Author(s):  
Xiao Chang ◽  
Marina Bakay ◽  
Yichuan Liu ◽  
Joseph Glessner ◽  
Komal S Rathi ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Multiple Testing ◽  
Snp Array ◽  
Genetic Effect ◽  
Pooled Analysis ◽  
Data Sets ◽  
Mtdna Haplogroups ◽  
Mitochondrial Dysfunctions ◽  
Reduced Risk

Abstract Background Neuroblastoma is a childhood malignancy that arises from the developing sympathetic nervous system. Although mitochondrial dysfunctions have been implicated in the pathophysiology of neuroblastoma, the role of mitochondrial DNA (mtDNA) has not been extensively investigated. Methods A total of 2404 Caucasian children diagnosed with neuroblastoma and 9310 ancestry-matched controls were recruited at the Children’s Hospital of Philadelphia. The mtDNA haplogroups were identified from SNP array data of two independent cohorts. We conducted a case-control study to explore potential associations of mtDNA haplogroups with the susceptibility of neuroblastoma. The genetic effect of neuroblastoma was measured by odds ratios (ORs) of mitochondrial haplogroups. All tests were two-sided. Results Haplogroup K was statistically significantly associated with reduced risk of neuroblastoma in the discovery cohort consisting of 1474 cases and 5699 controls (OR = 0.72, 95% confidence interval [CI] = 0.57 to 0.90; P = 4.8 × 10-3). The association was replicated in an independent cohort (OR = 0.69, 95% CI = 0.53 to 0.92; P = .01) of 930 cases and 3611 controls. Pooled analysis was performed by combining the two data sets. The association remained highly statistically significant after correction for multiple testing (OR = 0.71, 95% CI = 0.59 to 0.84, P = 1.96 × 10-4, Pcorrected = .002). Further analysis focusing on neuroblastoma subtypes indicated haplogroup K was more associated with high-risk neuroblastoma (OR = 0.57, 95% CI = 0.43 to 0.76; P = 1.46 × 10–4) than low-risk and intermediate-risk neuroblastoma. Conclusions Haplogroup K is an independent genetic factor associated with reduced risk of developing neuroblastoma in European descents. These findings provide new insights into the genetic basis of neuroblastoma, implicating mitochondrial DNA encoded proteins in the etiology of neuroblastoma.

scholarly journals Study of serum traditional and nontraditional biomarkers in Rheumatoid arthritis patients

2020 ◽  
Vol 11 (4) ◽  
pp. 7585-7592
Author(s):  
Vinod A N ◽  
Leena Chand ◽  
Preeti R Y ◽  
Harshitha S ◽  
Prahaladh R
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Markers ◽  
Cartilage Oligomeric Matrix Protein ◽  
Matrix Protein ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Sectional Study ◽  
Cross Sectional ◽  
Significant Difference

The study of biomarkers in Rheumatoid arthritis (RA) is highly indispensable to understand mechanisms of pathogenesis, diagnosis, prognosis, and treatment of disease. The role of traditional biomarkers like Anti-CCP, RF, and inflammatory markers like ESR and CRP is well established. In this study, we aimed to measure nontraditional biomarkers like Hyaluronic acid (HA), Cartilage oligomeric matrix protein (COMP), and Osteocalcin in the serum of RA patients and also to establish an association with traditional markers. It was a cross-sectional study involving 152 RA patients based on the 1987 ACR criteria for the diagnosis of RA and 68 age‑ and sex-matched healthy controls. After the clinical examination, traditional markers were assessed to measure the disease activity along with non traditional markers in RA patients. All the values were expressed as median (25th–75th percentile). In our study, there was a significant increase in serum HA levels in RA patients compared to healthy controls (p  < 0.03), whereas no significant difference in serum COMP and osteocalcin levels. The traditional inflammatory markers were significantly increased in RA patients than controls with (p  < 0.001). The serum HA levels were significantly correlated with traditional markers in RA patients. Conclusion: Significant increase in serum HA level in RA patients indicating synovial inflammation, but there were no notable changes in COMP and osteocalcin level in serum presuming the combination of these markers may be useful along with traditional markers in the different stages of RA.

scholarly journals Cytokines of the Th1 and Th2 type in sera of rheumatoid arthritis patients; correlations with anti-Hsp40 immune response and diagnostic markers.

2010 ◽  
Vol 57 (3) ◽  
Author(s):  
Stefan Tukaj ◽  
Agnieszka Kotlarz ◽  
Agnieszka Jóźwik ◽  
Zaneta Smoleńska ◽  
Ewa Bryl ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Healthy Controls ◽  
Flow Cytometric ◽  
Das 28 ◽  
Systemic Inflammatory Disease ◽  
Cytokine Levels ◽  
Shock Proteins ◽  
Cytometric Bead Array Assay ◽  
Inflammatory Effect

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease which affects approximately 1% of the population worldwide. Recent research on the role of heat shock proteins (Hsps) in RA development indicates that they may have pro- or anti-inflammatory effect, most probably via modulating cytokine secretion. We investigated type Th1 (INFγ, TNFα, IL-2) and type Th2 (IL-10, IL-6, IL-4) cytokine levels in sera of RA patients and healthy controls, using flow cytometric bead array assay, and searched for correlations between the cytokine levels and serum antibodies against bacterial (DnaJ) and human (Hdj1, Hdj2 and Hdj3) Hsp40 proteins, as well as clinical and laboratory parameters. The levels of all cytokines studied were significantly increased in RA patients; the highest increase relative to healthy controls (7-fold) was observed for IL-6 and its levels correlated positively with the antibodies directed to DnaJ and to the C-terminal domain of Hdj2, and with diagnostic parameters (DAS 28, Steinbrocker RTG criteria, ARA/7, ESR, TEN, SW and GH). INFγ levels correlated negatively with DAS 28, ESR, TEN and SW. No correlations were found for TNFα, IL-2 or IL-4. Our results support the hypothesis of Hsp40 involvement in RA as well as indicate that IL-6 serum level is a good marker of the RA activity.

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