scholarly journals Reduced Anti-Histone Antibodies and Increased Risk of Rheumatoid Arthritis Associated with a Single Nucleotide Polymorphism in PADI4 in North Americans

2019 ◽  
Vol 20 (12) ◽  
pp. 3093 ◽  
Author(s):  
Aisha M. Mergaert ◽  
Mandar Bawadekar ◽  
Thai Q. Nguyen ◽  
Laura Massarenti ◽  
Caitlyn L. Holmes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Nucleotide Polymorphism ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Rheumatoid Arthritis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Rheumatoid Arthritis Diagnosis ◽  
North Americans ◽  
Increased Risk ◽  
Citrullinated Proteins

Autoantibodies against citrullinated proteins are a hallmark of rheumatoid arthritis, a destructive inflammatory arthritis. Peptidylarginine deiminase 4 (PAD4) has been hypothesized to contribute to rheumatoid arthritis by citrullinating histones to induce neutrophil extracellular traps (NETs), which display citrullinated proteins that are targeted by autoantibodies to drive inflammation and arthritis. Consistent with this theory, PAD4-deficient mice have reduced NETs, autoantibodies, and arthritis. However, PAD4′s role in human rheumatoid arthritis is less clear. Here, we determine if single nucleotide polymorphism rs2240335 in PADI4, whose G allele is associated with reduced PAD4 in neutrophils, correlates with NETs, anti-histone antibodies, and rheumatoid arthritis susceptibility in North Americans. Control and rheumatoid arthritis subjects, divided into anti-cyclic citrullinated peptide (CCP) antibody positive and negative groups, were genotyped at rs2240335. In homozygotes, in vitro NETosis was quantified in immunofluorescent images and circulating NET and anti-histone antibody levels by enzyme linked immunosorbent assay (ELISA). Results were compared by t-test and correlation of rheumatoid arthritis diagnosis with rs2240335 by Armitage trend test. NET levels did not significantly correlate with genotype. G allele homozygotes in the CCP− rheumatoid arthritis group had reduced anti-native and anti-citrullinated histone antibodies. However, the G allele conferred increased risk for rheumatoid arthritis diagnosis, suggesting a complex role for PAD4 in human rheumatoid arthritis.

scholarly journals The functional −169T→C single-nucleotide polymorphism inFCRL3 is not associated with rheumatoid arthritis in white North Americans

2006 ◽  
Vol 54 (3) ◽  
pp. 1022-1025 ◽  
Author(s):  
Xiaolan Hu ◽  
Monica Chang ◽  
Randall K. Saiki ◽  
Michelle A. Cargill ◽  
Ann B. Begovich ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Nucleotide Polymorphism ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
North Americans

Single nucleotide polymorphism rs1128446 ТXNRD1 is a novel genetic marker of cerebral stroke

2021 ◽  
pp. 37-43
Author(s):  
О.Ю. Бушуева ◽  
А.В. Полоников ◽  
В.П. Иванов
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Ischemia Reperfusion ◽  
Basic Mechanism ◽  
Bioinformatic Analysis ◽  
Redox Status ◽  
Cerebral Stroke ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Thioredoxin System

Мозговой инсульт (МИ) занимает третье место в структуре смертности во всем мире и является ведущим фактором снижения когнитивных функций и деменции. Окислительный стресс является ведущим механизмом повреждения головного мозга при ишемии и последующей реперфузии. Тиоредоксиновая система является наиболее важным антиоксидантным барьером клетки, способным регулировать ее окислительно-восстановительный статус. Целью исследования было изучение ассоциации однонуклеотидного полиморфизма rs1128446 гена эндогенного регулятора тиоредоксина ТXNRD1 с риском развития МИ. Материалом для исследования послужила выборка неродственных жителей Центральной России общей численностью 825 человек. В исследование были включены 375 пациентов с МИ (216 мужчин, 159 женщин; средний возраст 59,44±0,51 лет). Контрольную группу составили 450 относительно здоровых индивидуумов (249 мужчин, 201 женщина, средний возраст 61,69±0,38 лет) без кардио- и цереброваскулярных заболеваний в анамнезе и имеющих нормальный уровень артериального давления. Генотипирование SNP проводили методом ПЦР в режиме реального времени путем дискриминации аллелей с помощью TaqMan-зондов. Для анализа ассоциаций генотипов с развитием заболевания пользовались лог-аддитивной регрессионной моделью. Все расчеты выполнены относительно минорного аллеля; введены поправки на пол и возраст. SNP rs1128446 ТXNRD1 был связан с повышенным риском развития МИ (OR=1,89; 95% CI=1,48-2,43; p<0,0001). Проведенный биоинформатический анализ выявил высокий регуляторный потенциал данного SNP в тканях сердечно-сосудистой системы. Таким образом, впервые установлена ассоциация rs1128446 ТXNRD1 с развитием МИ. Cerebral stroke (CS) is the leading factor in cognitive decline and dementia and ranks third in the structure of mortality worldwide. Oxidative stress is the basic mechanism of brain damage after cerebral ischemia-reperfusion. The thioredoxin system is the most important antioxidant barrier of the cell, capable of regulating its redox status. The aim of this study was to investigate the association of the common single nucleotide polymorphism rs1128446 in gene encoding the endogenous thioredoxin regulator TXNRD1 with the risk of CS. A total of 825 unrelated individuals from Central Russia were included for this study: 375 patients with CS (216 males, 159 females; 59.44±0.51 years old) and 450 healthy controls (249 males, 201 females, 61.69±0.38 years old). Genotyping was performed using TaqMan-based PCR. To analyze the associations of genotypes with the risk of diseases, a log-additive regression model was used. All calculations were performed relative to the minor allele; corrections for gender and age have been introduced. SNP rs1128446 TXNRD1 was associated with an increased risk of CS (OR=1.89; 95% CI=1.48-2.43; P<0.0001). Bioinformatic analysis revealed a high regulatory potential of this SNP in tissues of the cardiovascular system. Thus, for the first time, the association of rs1128446 TXNRD1 with the development of CS was revealed.

Genetic association of CCR5 promoter single nucleotide polymorphism in seronegative and seropositive rheumatoid arthritis

2012 ◽  
Vol 23 (2) ◽  
pp. 25-28
Author(s):  
Guadalupe Lima ◽  
Janette Furuzawa-Carballeda ◽  
Dolores Ramos-Bello ◽  
Juan Jakez-Ocampo ◽  
Virginia Pascual-Ramos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Nucleotide Polymorphism ◽  
Genetic Association ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Seropositive Rheumatoid Arthritis

A single nucleotide polymorphism of IL6-receptor is associated with response to tocilizumab in rheumatoid arthritis patients

2019 ◽  
Vol 19 (4) ◽  
pp. 368-374 ◽  
Author(s):  
Cécile Luxembourger ◽  
Adeline Ruyssen-Witrand ◽  
Chayma Ladhari ◽  
Cécile Rittore ◽  
Yannick Degboe ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Nucleotide Polymorphism ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

scholarly journals The correlation between methylenetetrahydrofolate reductase gene 677C > T polymorphism and fetal congenital defects: A meta-analysis

Pteridines ◽  
2020 ◽  
Vol 31 (1) ◽  
pp. 9-17
Author(s):  
Dexia Li ◽  
Enxia Wang ◽  
Xia Gao ◽  
Ping Li
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Publication Bias ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Random Effect ◽  
Congenital Defects ◽  
Nucleotide Polymorphism ◽  
Case Control Studies ◽  
Single Nucleotide ◽  
Increased Risk

AbstractObjective To investigate the correlation between the methylenetetrahydrofolate reductase (MTHFR) gene 677C> T polymorphism and fetal congenital defects.Method Original studies relevant to the MTHFR gene 677C>T single nucleotide polymorphism and fetal congenital defects were systematically searched in the electronic databases of Medline, EMBSE and China National Knowledge Infrastructure (CNKI). All relevant publications were screened for inclusion in the present work. The correlation between the MTHFR gene 677C > T single nucleotide polymorphism and the occurrence of fetal congenital defects was expressed as an odds ratio (OR) and its 95% confidence interval (95% CI). Publication bias was assessed by Begg’s funnel plot and Egger’s line regression test.Results Nineteen case-control studies were ultimately included in the present meta-analysis. The pooled results indicated that the general risk of fetal congenital defects was significantly elevated in subjects with the 677T allele of the MTHFR gene in dominant (OR=1.07,95%CI:1.03-1.12, P<0.05), homozygous (OR=1.17,95%CI:1.06-1.30, P<0.05) and recessive genetic models (OR=1.16,95%CI:1.03-1.31, P<0.05) through the random effect method. However, significant publication bias was identified upon pooling the individual data and evaluating the correlation.Conclusion According to the present evidence, the MTHFR gene 677C>T single nucleotide polymorphism is correlated with poor pregnancy outcomes, and subjects with the T allele have an increased risk of developing general fetal congenital defects.

The His155Tyr (489C>T) single nucleotide polymorphism of P2RX7 gene confers an enhanced function of P2X7 receptor in immune cells from patients with rheumatoid arthritis

2012 ◽  
Vol 276 (1-2) ◽  
pp. 168-175 ◽  
Author(s):  
Liliana Portales-Cervantes ◽  
Perla Niño-Moreno ◽  
Mariana Salgado-Bustamante ◽  
Mariana H. García-Hernández ◽  
Lourdes Baranda-Candido ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Nucleotide Polymorphism ◽  
Immune Cells ◽  
P2x7 Receptor ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

Disease Phenotypes and Gender Association of FCRL3 Single-Nucleotide Polymorphism −169T/C in Taiwanese Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis

2010 ◽  
Vol 38 (2) ◽  
pp. 264-270 ◽  
Author(s):  
JI-YIH CHEN ◽  
CHIN-MAN WANG ◽  
YEONG-JIAN JAN WU ◽  
SHIN-NING KUO ◽  
CHIUNG-FANG SHIU ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Single Nucleotide Polymorphism ◽  
Lupus Erythematosus ◽  
Nucleotide Polymorphism ◽  
Systemic Lupus ◽  
Single Nucleotide ◽  
Disease Phenotypes ◽  
And Gender ◽  
Non Destructive

Objective.To investigate the association of the functional FCRL3 single-nucleotide polymorphism (SNP) −169T/C with disease phenotypes and susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Taiwanese.Methods.FCRL3 SNP −169T/C was genotyped in 573 patients with SLE, 670 patients with RA, and 758 controls. Genotype distributions and allele frequencies were compared among the 3 groups as aggregates or as stratified by clinical characteristics, autoantibody profile, and sex within patient groups.Results.Overall, FCRL3 SNP −169T/C was not associated with susceptibility to either SLE or RA. However, −169CC genotype was significantly reduced in leukopenia-positive SLE patients as compared to the leukopenia-negative SLE patients (CC vs CT+TT, p = 6 × 10−4, OR 0.444, 95% CI 0.279–0.708) and controls (p = 6.1 × 10−3, OR 0.583, 95% CI 0.396–0.857). On the other hand, −169TT genotypes were significantly more numerous in RA patients with non-destructive disease as compared with patients with destructive disease (CC+CT vs TT: p = 0.007, OR 1.672, 95% CI 1.149–2.432). The −169T allele frequency was also significantly increased in non-destructive RA compared with patients with destructive disease (C vs T: p = 0.010, OR 1.423, 95% CI 1.089–1.859). FCRL3 SNP −169TT homozygous donors were significantly more numerous among female cyclic citrullinated peptide (CCP)-negative RA patients versus female CCP-positive RA patients (CC+CT vs TT: p = 0.019, OR 1.64, 95% CI 1.085–2.479).Conclusion.The functional FCRL3 SNP −169T/C appears to play important roles in the development of certain phenotypes such as SLE leukopenia and RA disease severity in Taiwanese patients with SLE and RA.

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