Association of pre-miRNA-146a rs2910164 and pre-miRNA-499 rs3746444 polymorphisms and susceptibility to rheumatoid arthritis

Hashemi, Mohammad; Eskandari-Nasab, Ebrahim; Zakeri, Zahra; Atabaki, Mahdi; Bahari, Gholamreza; Jahantigh, Mehdi; Taheri, Mohsen; Ghavami, Saeid

doi:10.3892/mmr.2012.1176

Cited by 86 publications

(62 citation statements)

References 50 publications

(70 reference statements)

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“…MiRNA-499 gene polymorphisms were investigated to be associated with ADs, however, the results are still debated. The homozygous genotype CC and allele C were found to be risk factors for predisposition to RA in Iranians [39]. The miRNA-499 polymorphism was discovered to be an independent factor of RA and was associated with RA risk, severity, and activity in Egyptian female patients [23].…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…One of the most important miRNAs, miR-499, regulates the expression of many cytokines, including IL-23a, IL-2R, IL-6, IL-2, and IL-18R (Hashemi et al, 2013). An important polymorphism with a change of A to G was identified (rs3746444) in the miR-499.…”

Section: Discussionmentioning

confidence: 98%

“…This polymorphism is located in the stem region of miR-499 and may damage the secondary structure stability and, in turn, disturb the miRNA maturation process and binding affinities to its target genes (Hu et al, 2009). It is reasonable that rs3746444 is correlated with risk of a variety of diseases such as different types of cancers (Xiang et al, 2012), RA (Hashemi et al, 2013), CAD (Zhou et al, 2012), and ischemic stroke (Luo et al, 2011). In contrast to the findings of Hashemi et al (2013), Yang et al (2012) did not detect a significant association between miR-499 rs3746444 polymorphism and RA.…”

Section: Discussionmentioning

confidence: 99%

Association of Pre-miRNA-499 rs3746444 and Pre-miRNA-146a rs2910164 Polymorphisms and Susceptibility to Behcet's Disease

Oner

Yenmiş

Tombultürk

et al. 2015

Genetic Testing and Molecular Biomarkers

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MiRNAs and NFKB1 are well-known immune response and inflammation regulators. MiRNA gene polymorphisms may affect miRNA biogenesis and function and, may thus, lead to changes in the expression of hundreds of genes such as NFKB1. The aim of this study was to investigate the association of Behcet's disease (BD) with NFKB1 rs28362491, pre-miRNA-146a rs2910164, and pre-miRNA-499 rs3746444 polymorphisms, as well as the analysis of their single and combined effects on its susceptibility in a Turkish population. These polymorphisms were analyzed by using the polymerase chain reaction-restriction fragment length polymorphism method in 100 BD patients and 145 healthy control subjects. The results were analyzed statistically using Pearson chi-square (χ(2)) test and Fisher's exact test (two sided). According to genotype analysis, the frequencies of ins/ins genotype and ins allele of rs28362491 were considerably higher in BD patients. Also, miRNA-499 rs3746444 homozygous (TT) genotypes exibited a significantly higher risk in patients with BD (odds ratios [OR]=3.0, 95% confidence intervals [95% CI]=1.284-7.007, p=0.017). Moreover, the frequency of T allele of rs3746444 was a risk factor for BD (OR=1.562, 95% CI=1.087-2.24, p=0.015). In addition, significant differences were found between the groups concerning miRNA-146a rs2910164 polymorphism. Homozygous CC genotype and C allele of rs2910164 polymorphism were found to be protective factors against BD. The results of the combined genotype analysis showed no notable differences between the multiple comparisons of rs28362491-rs2910164 and of rs28362491-rs3746444 in patients and control groups. Our data demonstrate that homozygous CC genotype and C allele of rs2910164 polymorphism are protective factors against BD, but rs3746444 and rs28362491 polymorphisms in miRNA-499 and in NFKB1 promoter are involved in the genetic susceptibility of BD. In addition, TT and ins/ins genotypes may influence certain proinflammatory cytokines and, may thus, play a role in the pathogenesis of BD.

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“…Exposure of cardiomyocytes to hypoxic and ischemic stress leads to down-regulation of miR-499 (Wang et al 2011). In addition, miR-499 regulates the expression of inflammatory cytokines, including IL-17Rβ, IL-23α, IL-2R, IL-6, IL-2 and IL-18R (Hashemi et al 2013). Rs3746444 is located in the stem region of the miR-499, and may damage the secondary structure stability and thus affect the miRNA maturation process and binding affinities to its target genes (Hu et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…It is reasonable that rs3746444 may contribute to the susceptibility to various diseases by regulating distinct sets of downstream genes. Many studies have shown that rs3746444 is correlated with risks of a variety of diseases, such as different types of cancer , rheumatoid arthritis (Hashemi et al 2013), CAD (Zhi et al 2012) and ischemic stroke . Previous studies revealed that the GG and AG genotypes of rs3746444 conferred increased risk for CAD (Zhi et al 2012) and ischemic stroke , respectively.…”

Section: Discussionmentioning

confidence: 99%

Association of microRNA Polymorphisms with the Risk of Myocardial Infarction in a Chinese Population

Chen

Hong

Chen

et al. 2014

Tohoku J. Exp. Med.

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MicroRNAs (miRNAs) are involved in the regulation of a variety of biological processes, such as inflammation. Dysregulation of miRNAs have been implicated in many human disease, including cardiovascular diseases. Polymorphisms in miRNA genes may affect the miRNA biogenesis and function, and thus cause changes in the expression of thousands of genes. The aim of this study was to examine whether miRNA polymorphisms (miR-146a rs2910164, miR-149 rs71428439, miR-196a2 rs11614913, miR-218 rs11134527, and miR-499 rs3746444) contribute to the risk for the development of myocardial infarction (MI). Five miRNA polymorphisms were genotyped in a total of 1808 subjects composed of 919 MI patients and 889 control individuals. The GG genotype of rs3746444 was found to be associated with a significantly increased risk of MI (recessive model, adjusted OR = 1.710, 95% CI: 1.058-2.763, P = 0.029). Although the CC genotype of rs2910164 significantly increased the risk of MI under dominant and additive models (P < 0.05), this difference disappeared after adjustment for age, sex, blood pressure, triglycerides, total cholesterol, HDL, LDL and diabetes. In addition, when rs3746444 and rs2910164 were evaluated together by the number of putative high-risk alleles, we found an increased risk of MI for subjects carrying 3-4 risk alleles (3-4 risk alleles vs. 0-1 risk allele, adjusted OR = 1.580, 95% CI: 1.069-2336, P = 0.022; 3-4 risk alleles vs. 0-2 risk allele, adjusted OR = 1.513, 95% CI: 1.031-2.219, P = 0.034). These findings indicate that miR-499 rs3746444 and miR-146a rs2910164 may represent novel markers of MI susceptibility.

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Association of pre-miRNA-146a rs2910164 and pre-miRNA-499 rs3746444 polymorphisms and susceptibility to rheumatoid arthritis

Cited by 86 publications

References 50 publications

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

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

Association of Pre-miRNA-499 rs3746444 and Pre-miRNA-146a rs2910164 Polymorphisms and Susceptibility to Behcet's Disease

Association of microRNA Polymorphisms with the Risk of Myocardial Infarction in a Chinese Population

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