scholarly journals PADI2 Polymorphisms Are Significantly Associated With Rheumatoid Arthritis, Autoantibodies Serologic Status and Joint Damage in Women from Southern Mexico

2021 ◽  
Vol 12 ◽  
Author(s):  
Iris Paola Guzmán-Guzmán ◽  
Claudia Isabel Ramírez-Vélez ◽  
Ramcés Falfán-Valencia ◽  
José Eduardo Navarro-Zarza ◽  
Ilse Adriana Gutiérrez-Pérez ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Manifestations ◽  
Joint Damage ◽  
Clinical Parameters ◽  
Nucleotide Polymorphisms ◽  
Southern Mexico ◽  
Single Nucleotide ◽  
The Family ◽  
Citrullinated Vimentin ◽  
Control Study

The enzymes of the family peptidylarginine deiminases (PADs) have an important role in the pathogenesis of rheumatoid arthritis (RA) due to their association with the anti-citrullinated protein antibodies (ACPA) production. To evaluate the association between single-nucleotide polymorphisms (SNPs) in the PADI2 gene and RA susceptibility, related clinical parameters, and the serologic status of autoantibodies in a women population with RA from southern Mexico, a case-control study was conducted (case n=229; control n=333). Sociodemographic characteristics were evaluated, along with clinical parameters, inflammation markers, the levels of ACPAs as anti-cyclic citrullinated peptides (anti-CCPs), anti-modified citrullinated vimentin (anti-MCV), and rheumatoid factor (RF). Genomic DNA was extracted from peripheral blood, and three SNPs of the PADI2 gene (rs1005753, rs2057094, and rs2235926) were performed by qPCR using TaqMan probes. The data analysis reveals that the carriers of the T allele for rs2057094 and rs2235926 presented an earlier onset of the disease (β= -3.26; p = 0.03 and β = -4.13; p = 0.015, respectively) while the carriers of the T allele for rs1005753 presented higher levels of anti-CCPs (β= 68.3; p = 0.015). Additionally, the T allele of rs2235926 was associated with a positive RF (OR = 2.90; p = 0.04), anti-MCV (OR = 2.92; p = 0.05), and with the serologic status anti-CCP+/anti-MCV+ (OR = 3.02; p = 0.03), and anti-CCP+/anti-MCV+/RF+ (OR = 3.79; p = 0.004). The haplotypes GTT (OR =1.52; p = 0.027) and TTT (OR = 1.32; p = 0.025) were associated with the presence of RA. In addition, in this study the haplotype TTT is linked to the presence of radiographic joint damage defined by a Sharp-van der Heijde score (SHS) ≥2 (OR = 1.97; p = 0.0021) and SHS ≥3 (OR = 1.94; p = 0.011). The haplotype TTT of SNPs rs1005753, rs2057094, and rs2235926 of the PADI2 gene confers genetic susceptibility to RA and radiographic joint damage in women from southern Mexico. The evidence reveals that SNPs of the PADI2 gene favors the presence of a positive serologic status in multiple autoantibodies and the clinical manifestations of RA at an early onset age.

scholarly journals Association of Leptin Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Sha-Sha Tao ◽  
Yi-Lin Dan ◽  
Guo-Cui Wu ◽  
Qin Zhang ◽  
Tian-Ping Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chinese Population ◽  
Clinical Manifestations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Significant Difference ◽  
Plasma Leptin

Background. Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. Methods. We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. Results. No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05 ). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05 ). No significant difference in plasma leptin levels was detected between RA patients and controls ( P > 0.05 ). Conclusion. Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.

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 FRI0452 THE IMPACT OF SINGLE NUCLEOTIDE POLYMORPHISMS IN ADORA2A AND ADORA3 ON THE EARLY RESPONSE TO METHOTREXATE AND PRESENCE OF THERAPY SIDE EFFECTS IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 823.1-823
Author(s):  
J. Roszkiewicz ◽  
D. Michałek ◽  
A. Ryk ◽  
B. Szmyd ◽  
E. Smolewska
Keyword(s):  
Rheumatoid Arthritis ◽  
Juvenile Idiopathic Arthritis ◽  
Side Effects ◽  
Disease Activity ◽  
Global Assessment ◽  
Disease Activity Score ◽  
Clinical Parameters ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Active Arthritis

Background:Juvenile idiopathic arthritis (JIA) is the most frequent rheumatic disease in children, with an estimated prevalence between 16 and 150 per 100 000 [1]. Methotrexate (MTX) administered at the dose 10-15mg/m2is currently recommended as the first-line treatment in most of JIA subtypes [2]. Despite its widespread use in rheumatology, the mechanism of MTX immunomodulatory action remains incompletely understood [3]. Free adenosine is one of the particles possibly associated with the action of MTX, acting via three types of adenosine receptor: ADORA2A, ADORA2B, and ADORA3 [4].Objectives:The aim of our study was to determine the association between single nucleotide polymorphisms inADORA2A(rs2236624, rs2298383) andADORA3(rs3393) receptors genes on the disease activity and presence of MTX therapy side effects in patients with JIA.Methods:One hundred children with JIA of all subtypes treated with MTX were recruited to the study. Demographic and clinical parameters were collected at the baseline of MTX therapy and on a control visit 4-6 months (median 5.09 months) after starting MTX. The clinical parameters included inflammatory markers values, number of joints with active arthritis, number of joints with restricted range of movement, physician’s global assessment of disease activity, parent/patient global assessment of overall well-being, functional ability (measured by the Childhood Health Assessment Questionnaire – CHAQ) and the value of Juvenile Idiopathic Arthritis Disease Activity Score 71 (JADAS 71). Presence of MTX side effects was evaluated on the control visit. SNP genotyping was performed using genomic DNA isolated from peripheral blood samples.Results:Both polymorphic variants ofADORA2A(rs2236624, rs2298383 - CC/CT) were significantly associated with 3.5 times higher odds of gastrointestinal side effects occurrence (OR: 3.52, 95%CI: 1.12-11.03, p=0.03 and OR: 3.49, 95%CI: 0.89-13.66 p=0.07) after adjustment to age, sex, dose and route of MTX administration. In addition, children with theADORA3rs3393 polymorphic variant (CT/CC) after six months of MTX treatment had significantly lower number of joints with active arthritis (0.0 vs 1.0, p=0.04), lower JADAS 71 score (3.0 vs 5.1, p=0.16) and lower value of CRP (0.6 vs 2.4, p=0.02).Conclusion:Although future studies are needed to verify our findings, polymorphisms inADORA2AandADORA3genes may become the determinants of MTX treatment efficacy and gastrointestinal toxicity in children with JIA.References:[1]Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001.J Rheumatol. 2004;31(2):390-392.[2]Ferrara G, Mastrangelo G, Barone P, et al. Methotrexate in juvenile idiopathic arthritis: advice and recommendations from the MARAJIA expert consensus meeting.PediatrRheumatol Online J. 2018;16(1):46. Published 2018 Jul 11. doi:10.1186/s12969-018-0255-8.[3]Brown, P. M., Pratt, A. G., & Isaacs, J. D. (2016). Mechanism of action of methotrexate in rheumatoid arthritis and the search for biomarkers. Nature Reviews Rheumatology, 12(12), 731–742. doi:10.1038/nrrheum.2016.175.[4]Varani, K. et al. A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release. Arthritis Res. Ther. 13, R197 (2011).Disclosure of Interests:None declared

scholarly journals ERAP1 association with ankylosing spondylitis is attributable to common genotypes rather than rare haplotype combinations

2017 ◽  
Vol 114 (3) ◽  
pp. 558-561 ◽  
Author(s):  
Amity R. Roberts ◽  
Louise H. Appleton ◽  
Adrian Cortes ◽  
Matteo Vecellio ◽  
Jonathan Lau ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Family Study ◽  
Nucleotide Polymorphisms ◽  
Rare Haplotype ◽  
Single Nucleotide ◽  
Haplotype Combination ◽  
Exact Test ◽  
The Family ◽  
Haplotype Frequencies

We investigated the proposal that ankylosing spondylitis (AS) is associated with unusual ERAP1 genotypes. ERAP1 haplotypes were constructed for 213 AS cases and 46 rheumatoid arthritis controls using family data. Haplotypes were generated from five common ERAP1 single nucleotide polymorphisms (SNPs)—rs2287987 (M349V), rs30187 (K528R), rs10050860 (D575N), rs17482078 (R725Q), and rs27044 (Q730E). Haplotype frequencies were compared using Fisher’s exact test. ERAP1 haplotypes imputed from the International Genetics of AS Consortium (IGAS) Immunochip study were also studied. In the family study, we identified only four common ERAP1 haplotypes (“VRNQE,” “MKDRQ,” “MRDRE,” and “MKDRE”) in both AS cases and controls apart from two rare (<0.5%) previously unreported haplotypes. There were no examples of the unusual ERAP1 haplotype combination (“*001/*005”) previously reported by others in 53% of AS cases. As expected, K528-bearing haplotypes were increased in the AS family study (AS 43% vs. control 35%), due particularly to an increase in the MKDRQ haplotype (AS 35% vs. control 25%, P = 0.01). This trend was replicated in the imputed Immunochip data for the two K528-bearing haplotypes MKDRQ (AS 33% vs. controls 27%, P = 1.2 × 10–24) and MKDRE (AS 8% vs. controls 7%, P = 0.004). The ERAP1 association with AS is therefore predominantly attributable to common ERAP1 haplotypes and haplotype combinations.

scholarly journals Association of rs3135500 and rs3135499 Polymorphisms in the MicroRNAbinding Site of Nucleotide-binding Oligomerization Domain 2 (NOD2) Gene with Susceptibility to Rheumatoid Arthritis

2021 ◽  
Author(s):  
Naeim Ehtesham ◽  
Behrang Alani ◽  
Deniz Mortazavi ◽  
Sara Azhdari ◽  
Taiebe Kenarangi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Responses ◽  
Nucleotide Binding ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Reactive Protein ◽  
Increased Risk ◽  
First Time ◽  
Control Study ◽  
Oligomerization Domain

The nucleotide-binding oligomerization domain 2 (NOD2) is the key regulator of inflammatory responses and has been involved in the pathogenesis of rheumatoid arthritis (RA). Laboratory and in silico evaluations have demonstrated that some polymorphisms in 3ˊUTR of NOD2 gene could influence the secondary structure of this region and similarly thermodynamic features of hybridization site and finally deregulate the expression of NOD2. In the current study, for the first time, we evaluated the possible association between single nucleotide polymorphisms (SNPs) rs3135500 and rs3135499 in the NOD2 gene with RA risk in the Iranian population. One hundred and fifteen patients with RA and 120 healthy subjects were recruited in this case-control study. Genotyping of rs3135500 and rs3135499 polymorphisms were accomplished using the real‑time polymerase chain reaction high resolution melting (HRM) method. We found a substantial association of AA and AG genotypes in rs3135500 with the risk of RA (AA vs GG; OR=5.547; 95%CI [2.564-11.999]; p<0.001 and AG vs GG; OR=2.179; 95%CI [1.145-4.147]; p=0.017). Moreover, in the patient group, there was a significant relationship between the increased concentration of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with rs3135500 (A allele) (p<0.05). However, there were no important associations between rs3135499 with the risk of RA (p>0.05). However, we found a noteworthy association of the C allele in rs3135499 with an increased level of CRP in patients (p>0.05). Our findings propose a considerable association between NOD2 polymorphisms with increased risk of RA and disease activity.

Nuclear receptors in disease: the oestrogen receptors

2004 ◽  
Vol 40 ◽  
pp. 157-167 ◽  
Author(s):  
Maria Nilsson ◽  
Karin Dahlman-Wright ◽  
Jan-Åke Gustafsson
Keyword(s):  
Nuclear Receptors ◽  
Target Genes ◽  
Receptor Subtype ◽  
Target Tissue ◽  
Oestrogen Receptors ◽  
Nucleotide Polymorphisms ◽  
Cell Type ◽  
Single Nucleotide ◽  
Beneficial Effects ◽  
The Family

For several decades, it has been known that oestrogens are essential for human health. The discovery that there are two oestrogen receptors (ERs), ERalpha and ERbeta, has facilitated our understanding of how the hormone exerts its physiological effects. The ERs belong to the family of ligand-activated nuclear receptors, which act by modulating the expression of target genes. Studies of ER-knockout (ERKO) mice have been instrumental in defining the relevance of a given receptor subtype in a certain tissue. Phenotypes displayed by ERKO mice suggest diseases in which dysfunctional ERs might be involved in aetiology and pathology. Association between single-nucleotide polymorphisms (SNPs) in ER genes and disease have been demonstrated in several cases. Selective ER modulators (SERMs), which are selective with regard to their effects in a certain cell type, already exist. Since oestrogen has effects in many tissues, the goal with a SERM is to provide beneficial effects in one target tissue while avoiding side effects in others. Refined SERMs will, in the future, provide improved therapeutic strategies for existing and novel indications.

Influence of the Acetylation Type on the Incidence of Isoniazid-Induced Hepatotoxicity in Patients with Newly Diagnosed Pulmonary Tuberculosis

2020 ◽  
Vol 65 (7-8) ◽  
pp. 31-36
Author(s):  
N. M. Krasnova ◽  
N. E. Evdokimova ◽  
A. A. Egorova ◽  
O. I. Filippova ◽  
E. A. Alekseeva ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Clinical Laboratory ◽  
Clinical Manifestations ◽  
Normal Activity ◽  
Slow Acetylators ◽  
Nucleotide Polymorphisms ◽  
Newly Diagnosed ◽  
Single Nucleotide ◽  
Tuberculosis Chemotherapy ◽  
Genetically Determined

Introduction. Liver damage can be a dangerous side effect of using isoniazid. Individual susceptibility to isoniazid in humans is dependent on the presence of N-acetyltransferase 2 allelic variants in genome. It was imperative to assess the effect of genetically determined isoniazid acetylation rate in terms of risk of developing isoniazid-induced hepatotoxicity, as well as prevention of potential hepatopathy, and improvement of tuberculosis chemotherapy safety. Aim. To study the effect of acetylation type on the incidence of isoniazid hepatotoxicity in residents of the Sakha Republic (Yakutia) with newly diagnosed pulmonary tuberculosis. Methods. The study included 112 patients with newly diagnosed pulmonary tuberculosis. Genotyping was performed using real-time polymerase chain reaction. The following single nucleotide polymorphisms were studied: rs1801280, rs1799930, rs1799931, rs1799929, rs1208, rs1041983. Hepatotoxicity was determined based on the results of clinical laboratory monitoring and using the criteria developed by the European Association for the Study of the Liver (2019). Results. Hepatotoxic reactions developed more often in slow acetylators (43.2%), compared to fast acetylators (20.7%) and intermediate acetylators (10.9%); p=0.002. Serum alanine aminotransferase activity was 5 or more times above the upper limit of normal activity in 37.8% of slow acetylators, and in 8.7% of intermediate acetylators; p=0.001. Clinical manifestations of isoniazid hepatotoxicity were observed more often in slow acetylators (29.7%), than in fast acetylators (3.4%); p=0.000. Conclusion. Slow acetylation type ought to be considered an important risk factor for developing isoniazid hepatotoxicity in patients with pulmonary tuberculosis.

scholarly journals Genetic polymorphism for IFNγ +874T/A in patients with acute toxoplasmosis

2012 ◽  
Vol 45 (6) ◽  
pp. 757-760 ◽  
Author(s):  
Elizabeth de Souza Neves ◽  
André Luis Land Curi ◽  
Maira Cavalcanti de Albuquerque ◽  
Cassius Schnel Palhano-Silva ◽  
Laura Berriel da Silva ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Case Control Study ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Nucleotide Polymorphism ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Duration Of Disease ◽  
Acute Toxoplasmosis ◽  
Control Study

INTRODUCTION: A single nucleotide polymorphism (SNP) in the gene encoding gamma interferon influences its production and is associated with severity of infectious diseases. This study aimed to evaluate the association of IFNγ+874T/A SNP with duration of disease, morbidity, and development of retinochoroiditis in acute toxoplasmosis. METHODS: A case-control study was conducted among 30 patients and 90 controls. RESULTS: Although statistical associations were not confirmed, A-allele was more common among retinochoroiditis cases and prolonged illness, while T-allele was more frequent in severe disease. CONCLUSIONS: Despite few cases, the results could indicate a relation between IFNγ+874T/A single nucleotide polymorphism and clinical manifestations of toxoplasmosis.

scholarly journals Impact of PD-1 gene polymorphism and its interaction with tea drinking on susceptibility to tuberculosis

2021 ◽  
Vol 149 ◽  
Author(s):  
Jing Wang ◽  
Mian Wang ◽  
Zihao Li ◽  
Xinyin Wu ◽  
Xian Zhang ◽  
...  
Keyword(s):  
Case Control Study ◽  
Preventive Measures ◽  
Nucleotide Polymorphisms ◽  
Unconditional Logistic Regression ◽  
Negative Interaction ◽  
Single Nucleotide ◽  
High Risk Populations ◽  
Tea Drinking ◽  
The Impact ◽  
Control Study

Abstract The aim of this study was to explore the impact of polymorphism of PD-1 gene and its interaction with tea drinking on susceptibility to tuberculosis (TB). A total of 503 patients with TB and 494 controls were enrolled in this case–control study. Three single-nucleotide polymorphisms of PD-1 (rs7568402, rs2227982 and rs36084323) were genotyped and unconditional logistic regression analysis was used to identify the association between PD-1 polymorphism and TB, while marginal structural linear odds models were used to estimate the interactions. Genotypes GA (OR 1.434), AA (OR 1.891) and GA + AA (OR 1.493) at rs7568402 were more prevalent in the TB patients than in the controls (P < 0.05). The relative excess risk of interaction (RERI) between rs7568402 of PD-1 genes and tea drinking was −0.3856 (95% confidence interval −0.7920 to −0.0209, P < 0.05), which showed a negative interaction. However, the RERIs between tea drinking and both rs2227982 and rs36084323 of PD-1 genes were not statistically significant. Our data demonstrate that rs7568402 of PD-1 genes was associated with susceptibility to TB, and there was a significant negative interaction between rs7568402 and tea drinking. Therefore, preventive measures through promoting the consumption of tea should be emphasised in the high-risk populations.

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