Association of rs2910164 polymorphism in MiR-146a gene with psoriasis susceptibility

Gong, Hai-bo; Zhang, Shilei; Wu, Xiujuan; Pu, Xiongming; Kang, Xiaojian

doi:10.1097/md.0000000000014401

Cited by 10 publications

(8 citation statements)

References 27 publications

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“…Of note, the previously performed bioinformatic analysis revealed that the G allele of this variant may enhance the stability of the pre-miRNA secondary structure, leading to a potential improvement of the miRNA maturation process and thus to an enhanced production of the resulting miRNAs [15]. This evidence is line with literature data showing an overexpression of MIR146A in Ps [22,28]. However, miR-146a has also been regarded as a negative regulator of inflammation, because it is able to target Interleukin 1 Receptor-Associated Kinase 1 (IRAK1, Xq28) and TNF Receptor-Associated Factor 6 (TRAF6, 11p12), that are well-known pro-inflammatory factors [29,30].…”

Section: Discussionsupporting

confidence: 88%

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RNAseq-Based Prioritization Revealed COL6A5, COL8A1, COL10A1 and MIR146A as Common and Differential Susceptibility Biomarkers for Psoriasis and Psoriatic Arthritis: Confirmation from Genotyping Analysis of 1417 Italian Subjects

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et al. 2020

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Psoriasis (Ps) and Psoriatic Arthritis (PsA) are characterized by a multifactorial etiology, involving genetic and environmental factors. The present study aimed to investigate polymorphisms (SNPs) within genes involved in extracellular matrix and cell homeostasis and microRNA genes as susceptibility biomarkers for Ps and PsA. Bioinformatic analysis on public RNA-seq data allowed for selection of rs12488457 (A/C, COL6A5), rs13081855 (G/T, COL8A1), rs3812111 (A/T, COL10A1) and rs2910164 (C/G, MIR146A) as candidate biomarkers. These polymorphisms were analyzed by Real-Time PCR in a cohort of 1417 Italian patients (393 Ps, 424 PsA, 600 controls). Statistical and bioinformatic tools were utilized for assessing the genetic association and predicting the effects of the selected SNPs. rs12488457, rs13081855 and rs2910164 were significantly associated with both Ps (p = 1.39 × 10−8, p = 4.52 × 10−4, p = 0.04, respectively) and PsA (p = 5.12 × 10−5, p = 1.19 × 10−6, p = 0.01, respectively). rs3812111, instead, was associated only with PsA (p = 0.005). Bioinformatic analysis revealed common and differential biological pathways involved in Ps and PsA. COL6A5 and COL8A1 take part in the proliferation and angiogenic pathways which are altered in Ps/PsA and contribute to inflammation together with MIR146A. On the other hand, the exclusive association of COL10A1 with PsA highlighted the specific involvement of bone metabolism in PsA.

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Section: Discussionsupporting

confidence: 88%

“…This variant is located within the miRNA seed region of miR-146a, encoded by the MIR146A gene. Several studies tried to investigate the association of this SNP with Ps, but results were conflicting [22]. In the present study, the G allele confers a higher susceptibility to Ps and PsA.…”

Section: Discussionmentioning

confidence: 64%

RNAseq-Based Prioritization Revealed COL6A5, COL8A1, COL10A1 and MIR146A as Common and Differential Susceptibility Biomarkers for Psoriasis and Psoriatic Arthritis: Confirmation from Genotyping Analysis of 1417 Italian Subjects

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et al. 2020

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“…Another study cited that susceptibility to pulmonary tuberculosis is not influenced by the MIR146A rs2910164 [ 48 ]. However, a meta-analysis approach on psoriasis case-control studies with rs2910164 revealed that the CC genotype is correlated with decreased risk of psoriasis [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Variants of MIRNA146A rs2910164 and MIRNA499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by Leishmania guyanensis and with plasma chemokine IL-8

et al. 2021

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Leishmania are intracellular protozoan parasites that cause a wide spectrum of clinical manifestations in genetically susceptible individuals with an insufficient or balanced Th1 immune response to eliminate the parasite. MiRNAs play important regulatory role in numerous biological processes including essential cellular functions. miR146-a acts as an inhibitor of interleukin 1 receptor associated kinase 1 (IRAK1) and tumour necrosis factor (TNF) receptor associated factor 6 (TRAF6) present in the toll-like receptors pathway while miR499a modulates TGF-β and TNF signalling pathways. Here, we investigated whether MIRNA146A rs2910164 and MIRNA499 rs3746444 variants are associated with the development of L. guyanensis (Lg)-cutaneous leishmaniasis (CL). The variants MIR146A rs2910164 and MIR499A rs3746444 were assessed in 850 patients with Lg-CL and 891 healthy controls by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Plasma cytokines were measured using the BioPlex assay. Carriers of rs2910164 CC genotype have 30% higher odds of developing CL (ORadjage/sex = 1.3 [95%CI 0.9–1.8]; Padjage/sex 0.14) compared to individuals with the genotype GG (ORadjage/sex = 0.77 [95%CI 0.56–1.0]; Padjage/sex 0.14) if exposed to Lg-infection. Heterozygous GC individuals also showed lower odds of developing CL (ORadjage/sex = 0.77 [95%CI 0.5–1.1]; Padjage/sex 0.09). Homozygosity for the allele C is suggestive of an association with the development of Lg-CL among exposed individuals to Lg-infection. However, the odds of developing CL associated with the CC genotype was evident only in male individuals (ORadjage = 1.3 [95% CI = 0.9–2.0]; Padjage = 0.06). Individuals homozygous for the G allele tend to have higher plasma IL-8 and CCL5. Similarly, for the MIR499A rs3746444, an association with the G allele was only observed among male individuals (OR = 1.4 [1.0–1.9]; P = 0.009). In a dominant model, individuals with the G allele (GG-GA) when compared to the AA genotype reveals that carriers of the G allele have 40% elevated odds of developing Lg-CL (ORadjage = 1.4 [1.1–1.9]). Individuals with the GG genotype have higher odds of developing Lg-CL (ORadjage/sex = 2.0 [95%CI 0.83–5.0]; Padjage = 0.01. Individuals homozygous for the G allele have higher plasma IL-8. Genetic combinations of both variants revealed that male individuals exposed to Lg bearing three or four susceptible alleles have higher odds of developing Lg-CL (OR = 2.3 [95% CI 1.0–4.7]; p = 0.017). Both MIR146A rs2910164 and MIR499A rs3746444 are associated with the development of Lg-CL and this association is prevalent in male individuals.

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“…49,131 Polymorphisms that affect miR-146a expression was described as predisposing factors for many autoimmune diseases, including psoriasis. [141][142][143] MiRNAs are also involved in the regulation on other immune cell types. For example, Meng et al reported that miR-148a is a key modulator of moDC differentiation in psoriasis.…”

Section: Mir-155 Expression Is Increased Upon T-cell Activation and R...mentioning

confidence: 99%

The role of microRNA in psoriasis: A review

Jiang

Shi

et al. 2023

Experimental Dermatology

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Psoriasis is a chronic immune‐mediated inflammatory skin disease that involves a complex interplay between infiltrated immune cells and keratinocytes. Great progress has been made in the research on the molecular mechanism of coding and non‐coding genes, which has helped in clinical treatment. However, our understanding of this complex disease is far from clear. MicroRNAs (miRNAs) are small non‐coding RNA molecules that are involved in post‐transcriptional regulation, characterised by their role in mediating gene silencing. Recent studies on miRNAs have revealed their important role in the pathogenesis of psoriasis. We reviewed the current advances in the study of miRNAs in psoriasis; the existing research has found that dysregulated miRNAs in psoriasis notably affect keratinocyte proliferation and/or differentiation processes, as well as inflammation progress. In addition, miRNAs also influence the function of immune cells in psoriasis, including CD4+ T cells, dendritic cells, Langerhans cells and so on. In addition, we discuss possible miRNA‐based therapy for psoriasis, such as the topical delivery of exogenous miRNAs, miRNA antagonists and miRNA mimics. Our review highlights the potential role of miRNAs in the pathogenesis of psoriasis, and we expect more research progress with miRNAs in the future, which will help us understand this complex skin disease more accurately.

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Association of rs2910164 polymorphism in MiR-146a gene with psoriasis susceptibility

Cited by 10 publications

References 27 publications

RNAseq-Based Prioritization Revealed COL6A5, COL8A1, COL10A1 and MIR146A as Common and Differential Susceptibility Biomarkers for Psoriasis and Psoriatic Arthritis: Confirmation from Genotyping Analysis of 1417 Italian Subjects

RNAseq-Based Prioritization Revealed COL6A5, COL8A1, COL10A1 and MIR146A as Common and Differential Susceptibility Biomarkers for Psoriasis and Psoriatic Arthritis: Confirmation from Genotyping Analysis of 1417 Italian Subjects

Variants of MIRNA146A rs2910164 and MIRNA499 rs3746444 are associated with the development of cutaneous leishmaniasis caused by Leishmania guyanensis and with plasma chemokine IL-8

The role of microRNA in psoriasis: A review

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