Association of microRNAs genes polymorphisms with rheumatoid arthritis in Egyptian female patients

El‐Shal, Amal S.; Aly, Nader M.; Galil, Sahar M. Abdel; Moustafa, Mohamed A.; Kandel, Wael A

doi:10.1016/j.jbspin.2013.03.005

Cited by 43 publications

(44 citation statements)

References 33 publications

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“…As for the miR - 146a SNP, some associations with pathogenesis of rheumatic diseases have been described especially for patients with ankylosing spondylitis in a Han Chinese population (Xu et al 2015). However, this SNP has not been reported to be associated with RA in either Asian or Caucasian populations (Chatzikyriakidou et al 2010; El-Shal et al 2013; Zhou et al 2015; the present study). Although, in a study of Zhou et al (2015), a significant association of the GG genotype with RA in females was observed, while the CC homozygosity seemed to be correlated with the DAS28 score.…”

Section: Discussioncontrasting

confidence: 67%

Significance of Polymorphism and Expression of miR-146a and NFkB1 Genetic Variants in Patients with Rheumatoid Arthritis

Bogunia‐Kubik

Wysoczańska

Piątek

et al. 2016

Arch. Immunol. Ther. Exp.

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MicroRNA-146a (miR-146a) has been shown to play an important role in the regulation of inflammatory innate immune responses, and found to be differentially expressed in rheumatoid arthritis (RA). Through NF-κB pathway, this molecule is able to stimulate the release of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-17. It has been also suggested that single-nucleotide polymorphisms (SNPs) in miRNA sequences may alter miRNA expression and that miR-146a rs2910164 SNP may contribute to RA development. These observations prompted us to analyze the potential associations between the miR-146a-3p (rs2910164, G > C) and NFkB1 (rs28362491, ins/del ATTG) polymorphisms and miR-146a-5p expression in patients’ sera in relation to clinical outcome of the treatment as well as predisposition to RA. Genotyping was performed in 111 patients and 130 healthy individuals while 16 controls and 13 RA patients (before and after three months of therapy with TNF-α inhibitors (TNFi)) were studied for the circulating miR-146a-5p serum expression level. Patients carrying the NFkB1 ins/ins genotype were characterized by worse response to TNFi treatment (p = 0.023). In patients, before TNFi therapy, expression levels of miR-146a-5p were less (0.422 ± 0.171) as compared to those detected after three months of treatment (1.809 ± 0.658, p = 0.033) and observed for healthy controls (5.302 ± 2.112, p = 0.048). Moreover, patients with higher circulating miR-146a-5p levels after three months of TNFi administration were more frequently carrying the rs2910164-C allele (p = 0.032). These results support the hypothesis that miR-146a might be involved in pathogenesis of RA and imply that miR-146a-3p polymorphism may be associated with miR-146a-5p levels in serum after anti-TNF-α treatment.

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Section: Discussioncontrasting

confidence: 67%

Significance of Polymorphism and Expression of miR-146a and NFkB1 Genetic Variants in Patients with Rheumatoid Arthritis

Bogunia‐Kubik

Wysoczańska

Piątek

et al. 2016

Arch. Immunol. Ther. Exp.

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“…As protein-encoding genes, miRNA-encoding genes can be affected by nucleotide single polymorphisms (SNPs) that could affect their expression levels in disease. For example, the rs3746444 located in pre-miR-499 is associated with clinical markers of inflammation and disease severity in RA patients [9,10]. On the other hand, “silent” mutation in protein-encoding genes can alter miRNA function, as a synonymous variant in the IRGM gene impairs the binding of miR-196 and increases the risk for Crohn’s disease [11].…”

Section: Introductionmentioning

confidence: 99%

X-Linked miRNAs Associated with Gender Differences in Rheumatoid Arthritis

Khalifa

Pers

Ferreira

et al. 2016

IJMS

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Rheumatoid arthritis (RA) is an autoimmune disease that predominantly affects women. MicroRNAs have emerged as crucial regulators of the immune system, whose expression is deregulated in RA. We aimed at quantifying the expression level of 14 miRNAs located on the X chromosome and at identifying whether differences are associated with disease and/or sex. A case–control study of 21 RA patients and 22 age- and sex-matched healthy controls was performed on peripheral blood mononuclear cells. The expression level of five miRNAs (miR-221, miR-222, miR-532, miR-106a, and miR-98) was significantly different between RA and controls when stratifying by sex, and the expression level of four miRNAs (miR-222, miR-532, miR-98, and miR-92a) was significantly different between RA females and males. The expression quantitative trait loci (eQTL) analysis revealed a significant gender effect of the FoxP3 promoter polymorphism rs3761548A/C on miR-221, miR-222 and miR-532 expression levels, and of the FoxP3 polymorphism rs2232365A/G on miR-221 expression levels in PBMC of RA patients. These data further support the involvement of the X chromosome in RA susceptibility. X-linked miRNAs, in the context of sex differences, might provide novel insight into new molecular mechanisms and potential therapeutic targets in RA for disease treatment and prevention.

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“…While in contrast, other two studies observed no significant differences in miRNA-146a genotype distribution in Chinese female RA patients compared to male RA patients [23] and in Egyptian female patients compared to controls [24]. Moreover, the later study of Egyptian female RA patients reported no significant differences in all disease severity and activity parameters among different miRNA-146a genotype [24]. Studies specified that miRNA-146a is a critical manager in RA evolution as it can drive a negative feedback mechanism to prevent excess inflammation [25, 26].…”

Section: Discussionmentioning

confidence: 94%

“…It was evidenced that estrogen could regulates miRNA-146a expression in immune cells, and miRNA-146a plays an important role in estrogen-mediated immune regulation [22]. While in contrast, other two studies observed no significant differences in miRNA-146a genotype distribution in Chinese female RA patients compared to male RA patients [23] and in Egyptian female patients compared to controls [24]. Moreover, the later study of Egyptian female RA patients reported no significant differences in all disease severity and activity parameters among different miRNA-146a genotype [24].…”

Section: Discussionmentioning

confidence: 99%

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Association of MiRNA-146a, MiRNA-499, IRAK1 and PADI4 Polymorphisms with Rheumatoid Arthritis in Egyptian Population

Shaker

El-Boghdady

Sayed³

2018

Cell Physiol Biochem

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Background/Aims: Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting up to 1% of the population worldwide. The aim of the present study was to investigate whether miRNA-146a rs2910164, miRNA-499 rs3746444, IRAK1 rs3027898 and PADI4 rs1748033 polymorphisms are associated with susceptibility to RA in Egyptians and whether they influence disease severity and activity. Methods: The study was performed on 104 unrelated RA patients and 112 healthy subjects. RA patients were further subdivided into active and inactive RA groups. Polymorphisms were genotyped by using real-time polymerase chain reaction with TaqMan allelic discrimination assay. Results: Significant differences in the frequency of miRNA-146a rs2910164, miRNA-499 rs3746444, IRAK1 rs3027898 and PADI4 rs1748033 alleles and genotypes were observed between RA patients and controls. Only CA and AA genotypes of IRAK1 rs3027898 shows a significant difference between active and inactive subgroups. MiRNA-146a rs2910164 and IRAK1 rs3027898 polymorphisms were a risk factor for predisposition to RA in codominant and dominant tested inheritance models, while, the miRNA-499 rs3746444 and PADI4 rs1748033 polymorphisms were a risk factor in codominant and recessive one. CG and GG genotypes of miRNA-146a rs2910164 were associated with positive erosions. CA genotype of IRAK1 rs3027898 was associated with low disease activity and negative erosions, while, the AA genotype was associated with high disease activity. CC genotype of PADI4 rs1748033 was associated with negative rheumatoid factor. Conclusion: The 4 studied SNPs were likely to play an important role in the susceptibility to RA and can influence disease severity and activity in Egyptian population.

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Association of microRNAs genes polymorphisms with rheumatoid arthritis in Egyptian female patients

Cited by 43 publications

References 33 publications

Significance of Polymorphism and Expression of miR-146a and NFkB1 Genetic Variants in Patients with Rheumatoid Arthritis

Significance of Polymorphism and Expression of miR-146a and NFkB1 Genetic Variants in Patients with Rheumatoid Arthritis

X-Linked miRNAs Associated with Gender Differences in Rheumatoid Arthritis

Association of MiRNA-146a, MiRNA-499, IRAK1 and PADI4 Polymorphisms with Rheumatoid Arthritis in Egyptian Population

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