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Impact of MTHFR gene polymorphism on the outcome of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients
Abstract<p>Analyze the relationship between genetic variations in the MTHFR gene at SNPs (rs1801131 and rs1801133) and the therapy outcomes for Iraqi patients with rheumatoid arthritis (RA). The study was conducted on a cohort of 95 RA Iraqi patients. Based on their treatment response, the cohort was divided into two groups: the responder (47 patients) and the nonresponder (48 patients), identified after at least three months of methotrexate (MTX) treatment. A polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) technique was employed to analyze the MTHFR variations, specifically at rs1801133 and rs1801131. Overall, rs1801131 followed both codominant and dominate models, in which in the codominant model, GG [OR (95% CI) 0.11 (0.022–0.553)] and TG [OR (95% CI) 0.106 (0.021–0.528)] predict responders compared to the TT genotype; meanwhile, for the dominate model, the presence of both GG and TG genotypes [OR (95% CI) 0.108 (0.023–0.507)] together predict responders compared to the TT genotype. The A<sub>rs1801133</sub>G<sub>rs1801131</sub> haplotype was significantly associated with responders [OR (95% CI): 0.388 (0.208–0.723)], while the G<sub>rs1801133</sub>T<sub>rs1801131</sub> haplotype was associated marginally with nonresponders [OR (95% CI) 1.980 (0.965–4.064)]. In the final multivariate analysis, GG/TG<sub>rs1801131</sub> genotypes were independently related to responders after adjustment for patients, disease, and treatment characteristics, while TT<sub>rs1801131</sub> genotypes were associated with nonresponders. The Iraqi RA patients showed genetic polymorphism in MTHFR gene rs1801131 with T carrier allele associated with nonresponders to MTX therapy. The rs1801131 followed both codominant and dominant models. The G-carried allele for rs1801131 showed an independent association with responder to MTX therapy after adjustment for patients, disease, and treatment characteristics.</p>
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Publication Date
Fri Jun 07 2024
Journal Name
Medicine
Impact of TYMS gene polymorphism on the outcome of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients – identification of novel single nucleotide polymorphism: Cross-sectional study

The current work aims to evaluate the association between genetic mutations in thymidylate synthetase (TYMS gene in exon1 and partial regions of promotor and intron 1 [877 bp, 657,220–658,096 bp]) and the therapeutic outcomes for rheumatoid arthritis (RA) Iraqi patients. An observational cross-sectional study involving 95 RA patients with established RA patients based on their methotrexate treatment responsiveness. Genetic sequencing of the TYMS gene was performed for all patients according to the instruction manuals of the sequencing company (Macrogen Inc. Geumchen, South Korea). Four polymorphisms were identified by sequencing 95 randomly selected patients in the noncoding region of TYMS

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Publication Date
Tue Feb 27 2024
Journal Name
Pharmacia
Association of the rs1801133 and rs1801131 polymorphisms in the MTHFR gene and the adverse drug reaction of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients

Background: Methotrexate is one of the mainstays for treating rheumatoid arthritis (RA) with a wide range of adverse drug reactions, however, it’s the relationship between adverse drug reactions and genetic polymorphism remains to be highlighted, and there is a lack of studies concerning Arabic Iraqi population regarding this aspect.

Objective: Evaluate the association between genetic mutations in the MTHFR gene in SNPs (rs1801133G&gt;A and rs1801131T&gt;G) on the adverse drug reaction for RA Iraqi patients.

Methods: An observational study, that involved 95 Iraqi RA patients with established RA. Patien

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Publication Date
Fri Dec 30 2022
Journal Name
Iraqi Journal Of Science
MTHFR Gene Polymorphisms in Iraqi Kurdish Rheumatoid Arthritis Patients: Relation to Methotrexate Response and Toxicity

     Methotrexate (MTX) is still one of the gold standard treatments for rheumatoid arthritis (RA). It shows diverse outcomes in blood level and clinical response, this was demonstrated by its relation to the genetic polymorphism in the pharmacogenetic study. This study aimed to investigate the role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in relation to MTX efficacy and toxicity in Iraqi Kurdish RA patients. Sixty-four RA patients were involved in this study with an average age of 47.78 ±14.08 and female to male ratio of (8.1). Diagnosis and disease activity were confirmed. Blood analyses, including those of laboratory markers of disease activity, were done. The 28 joint disease activity score (DAS28-CRP) w

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Publication Date
Sun Jun 03 2018
Journal Name
Baghdad Science Journal
Gene Expression and Polymorphism of Interleukin-4 in a Sample of Iraqi Rheumatoid Arthritis Patients

It was aimed to understand the interleukin-4 (IL-4) role in etio-pathogenesis of rheumatoid arthritis (RA). Two approaches were adopted. In the first one, a quantitative expression of IL4 gene was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and such findings were correlated with some demographic, clinical and laboratory parameters, which included gender, duration of disease, disease activity score (DAS-28), rheumatoid factors (RFs), C-reactive protein (CRP) and anti-cyclic citrullinated peptide (ACCP) antibodies. In the second approach, a single nucleotide polymorphism (SNP) of IL4 gene (rs2243250) was inspected by DNA sequencing using specific primers. Fifty-one Iraqi RA patients (22 males and 29 fem

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Publication Date
Sun Jan 30 2022
Journal Name
Iraqi Journal Of Science
Single Nucleotide Polymorphism of Padi4 Gene )Rs11203367( in A Sample of Rheumatoid Arthritis Iraqi Patients

     Rheumatoid arthritis (RA) is an inflamed chronic autoimmune disease in which genetics and environment are the most common causative factors. Peptidyl arginine deiminase type IV (PADI4) is an enzyme responsible for the posttranslational conversion of arginine residues into citrulline. Real-time polymerase chain reaction (RT-PCR) is a specific technique was used to determine gene polymorphism. One hundred twenty three patients molecularly confirmed with RA and sixty healthy control subjects were recruited. By applying the logistic regression analysis, some alleles and genotypes were associated with susceptibility to RA. Under the allelic model, C allele frequency was significantly increased in RA patients compared

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Publication Date
Wed Jun 27 2018
Journal Name
Iraqi Journal Of Science
Single Nucleotide Polymorphism of IL1B Gene (rs16944) in a Sample of Rheumatoid Arthritis Iraqi Patients

Cytokines play a prominent role in etiology and pathogenesis of rheumatoid arthritis (RA), and one of these cytokines is interleukin-1β (IL-1β). The association between IL1B gene single nucleotide polymorphism (SNP: rs16944) and rheumatoid arthritis (RA) in a sample of Iraqi patients was investigated. Fifty-one RA patients (21 males and 30 females) were enrolled and their age range was 20 - 63 years (44.9 ± 1.5 years). In addition to patients, 45 apparently healthy control subjects were also enrolled in the study. They matched patients for ethnicity (Iraqis), gender (14 males and 31 females) and age (41.3 ± 1.3 years). Analysis of Hardy-Weinberg equilibrium (HWE) in RA patients and controls revealed that the IL1B ge

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Publication Date
Sun Jan 01 2023
Journal Name
The Egyptian Journal Of Hospital Medicine
Association of Interleukin-12B Polymorphism and Serum Level of Interleukin-12 in a Sample of Iraqi Patients with Rheumatoid Arthritis

Background In rheumatoid arthritis, your immune system attacks the tissue lining the joints on both sides of your body. Other parts of the body may also be affected. Unsure of the exact cause. Two separate genes termed IL12A (p35) and IL12 encode the heterodimeric cytokine known as IL12 (p40). Several different hematopoietic cell types can have several different hematopoietic cell types that can generate antigen-presenting cells (APCs), including DCs and macrophages. Objectives This study aimed to investigate if the interleukin IL-12B gene's common polymorphisms in an Iraqi population were associated with RA. Material and methods Blood samples were taken from 70 Iraqi patients with RA illnesses and 30 Iraqi controls during the periods from

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Publication Date
Sun Dec 22 2019
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
The Belief about Medicines among a Sample of Iraqi Patients with Rheumatoid Arthritis

Rheumatoid arthritis is a chronic, progressive, inflammatory autoimmune disease of unidentified etiology, associated with articular, extra-articular and systemic manifestation that require long-standing treatment. Taking patient’s beliefs about the prescribed medication in consideration had been shown to be an essential factor that affects adherence of the patient in whom having positive beliefs is an essential for better adherence. The purpose of the current study was to measure beliefs about medicines among a sample of Iraqi patients with Rheumatoid arthritis and to determine possible association between this belief and some patient-certain factors. This study is a cross-sectional study carried out on 250 already diagnosed rheumatoid

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Publication Date
Fri May 24 2013
Journal Name
American Journal Of Pharmacological Sciences
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Publication Date
Sat Sep 30 2023
Journal Name
Romanian Journal Of Rheumatology
Association between genetic polymorphism in tumor necrosis factor-alpha gene and adverse effects of etanercept in rheumatoid arthritis patients

Background. Gene polymorphisms affect etanercept’s pharmacokinetics, pharmacodynamics, and side effects. This effect is evidenced by the extensive genetic variation in the drug’s targets. Objectives. This study aims to find the association between different genotypes of the promoter region of the TNF-α gene at -308G/A(rs1800629), -857C/T(rs1799724), -863 C/A(rs1800630), -1031 T/C (rs1799964), -806 C/T (rs4248158) and -376 G/A (rs1800750) and the side effects of ETN that occurred to Iraqi RA patients. Method. The trial included patients with rheumatoid arthritis who had been using ETN for at least six months. The participants were from the Baghdad Teaching Hospital Rheumatology Unit. The PCR was sequenced to determine the polymo

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