Allele-Specific Targeting of microRNAs to HLA-G and Risk of Asthma

Tan, Zheng; Randall, Glenn; Fan, Junmei; Camoretti-Mercado, Blanca; Brockman-Schneider, Rebecca; Lin, Pao‐Hwa; Solway, Julian; Gern, James E.; Lemanske, Robert F.; Nicolae, Dan L.; Ober, Carole

doi:10.1086/521200

Cited by 347 publications

(296 citation statements)

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“…In our case-control study, we identified a strong association (P=0.0004) between rs12731181 and essential by guest on May 11, 2018 http://atvb.ahajournals.org/ Downloaded from hypertension in the Han Chinese population in both men and women. Moreover, carriers with the risk G allele exhibited elevated expression of FP in peripheral tissues and had significantly higher SBP and DBP than individuals with the AA genotype.…”

Section: Discussionmentioning

confidence: 72%

“…12 SNPs in miRNA-target sites in the 3′UTR of genes represent a specific class of functional polymorphisms and may lead to the dysregulation of post-transcriptional gene expression by disrupting regulatory miRNA binding. 13 An increasing number of 3′UTR SNPs in miRNA binding sites have been found to be associated with a variety of complex human diseases, such as hypertension, 14 cancer, 15 Tourette syndrome, 16 asthma, 17 and Parkinson disease. 18 Recently, a European genome-wide association study reported that the SNP rs12731181, located in the FP 3′UTR, may be associated with increased risk for hypertension in individuals from southern Germany (P=2.5×10 -4 ), but this association was not replicated in other European populations.…”

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confidence: 99%

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Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F _2α Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese Population

Xiao

Plewczynski

et al. 2015

ATVB

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P rostanoids are biologically active derivatives of arachidonic acid that is released from membrane phospholipids and then converted through cyclooxygenase metabolism. These lipid mediators play an important role in blood pressure (BP) homeostasis. Both traditional nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 selective nonsteroidal antiinflammatory drugs can elevate BP in patients. 1 Vasodilator prostanoids, such as prostaglandin (PG) I 2 and PGE 2 , are essential for regulating renal blood flow and mediating salt/ water reabsorption in the kidney.2,3 Deletion of the PGI 2 receptor or the PGE 2 receptor subtype 2 (EP2) results in saltsensitive hypertension. 4,5 However, inactivation of the PGE 2 receptor subtypes 1 and 3 (EP1 and EP3, respectively) reduces chronic angiotensin-II-driven hypertension and attenuates the angiotensin-II pressor response by reducing arterial contractility. 6,7 The levels of PGF 2α , a vasoconstrictor, are augmented © 2015 American Heart Association, Inc. Objective-To investigate whether rs12731181 (A→G) interrupted miR-590-3p-mediated suppression of the prostaglandin F 2α receptor (FP) and whether it is associated with essential hypertension in the Chinese population. Approach and Results-We found that miR-590-3p regulates human FP gene expression by binding to its 3′-untranslated region. rs12731181 (A→G) altered the binding affinity between miR-590-3p and its FP 3′-untranslated region target, thus reducing the suppression of FP expression, which, in turn, enhanced FP receptor-mediated contractility of vascular smooth muscle cells. Overexpression of FP augmented vascular tone and elevated blood pressure in mice. An association study was performed to analyze the relationship between the FP gene and essential hypertension in the Han Chinese population. The results indicated that the rs12731181 G allele was associated with susceptibility to essential hypertension. Carriers of the AG genotype exhibited significantly higher blood pressure than those of the AA genotype. FP gene expression was significantly higher in human peripheral leukocytes from individuals with the AG genotype than that in leukocytes from individuals with the AA genotype. Conclusions-rs12731181 in the seed region of the miR-590-3p target site is associated with increased risk of essential hypertension and represents a new paradigm for FP involvement in blood pressure regulation. in circulation under the conditions that increase cardiovascular risks, for example, after chronic high-salt intake, smoking, and hypercholesterolemia. 8 The PGF 2α receptor (FP) is highly expressed in distal convoluted tubules and cortical collecting ducts in the kidney and mediates water absorption.9 FP is also present in resistance arterioles that are involved in regulating the vasopressor response.8 Thus, ablation of FP induces hypotension and retards atherosclerosis in low-density lipoprotein receptor-knockout mice. 10MicroRNAs (miRNAs), ≈22 single-stranded nucleotide RNA molecules, play an important gene-regulatory function mo...

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Section: Discussionmentioning

confidence: 72%

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confidence: 99%

Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F _2α Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese Population

Xiao

Plewczynski

et al. 2015

ATVB

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“…MiRNAs are involved in diverse biological processes, including development, stress response, cancer, and cardiac hypertrophy, implicating them in normal and pathological processes (8). However, to the best of our knowledge, studies relevant to asthma or asthma risk are still lacking, except for a recent report demonstrating that a single nucleotide polymorphism at the 3' untranslated region of HLA-G, an asthma-susceptibility gene, affects the binding of three miRNAs to this gene (9). Allergic airway inflammation may be particularly sensitive to miRNA regulation since it is characterized by marked changes in gene and protein expression in the lung (10–12).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-21 Is Up-Regulated in Allergic Airway Inflammation and Regulates IL-12p35 Expression

Munitz²,

Rothenberg³

2009

The Journal of Immunology

526

456

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Allergic airway inflammation is characterized by marked in situ changes in gene and protein expression, yet the role of microRNAs (miRNAs), a new family of key mRNA regulatory molecules, in this process has not yet been reported. Using a highly sensitive microarray based approach, we identified 21 miRNAs with differential expression between doxycycline-induced lung-specific IL-13 transgenic mice (with allergic airway inflammation) and control mice. In particular, we observed over-expression of miR-21 and under-expression of miR-1 in the induced IL-13 transgenic mice compared to control mice. These findings were validated in two independent models of allergen-induced allergic airway inflammation and in IL-4 lung transgenic mice. While IL-13 induced miR-21 expression was IL-13 receptor alpha 1 dependent, allergen induced miR-21 expression was mediated mainly independent of IL-13 receptor alpha 1 and STAT6. Notably, predictive algorithms identified potential direct miR-21 targets among IL-13-regulated lung transcripts such as IL-12p35 mRNA that was decreased in IL-13 transgenic mice. Introduction of pre-miR-21 dose-dependently inhibited cellular expression of a reporter vector harboring the 3’UTR of IL-12p35. Moreover, mutating miR-21 binding sites in IL-12p35 3’UTR abrogated miR-21 mediated repression. In summary, we have identified a miRNA signature in allergic airway inflammation, which includes miR-21 that modulates IL-12, a molecule germane to T helper cell polarization.

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“…Moreover, at the 3'-UTR, a 14-bp ins/del has been widely reported as causing mRNA instability (rs371194629) (Rousseau et al, 2003). The presence of a G allele at rs1063320 (3142C>G) is known to increase the site affinity for microRNA, favoring mRNA degradation (Tan et al, 2007). Being upstream of an AU-rich motif involved in mRNA degradation, the A allele at rs9380142 (3187A>G) decreases HLA-G expression (Yie et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

HLA-G genetic variants and hepatocellular carcinoma: a meta-analysis

et al. 2016

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Allele-Specific Targeting of microRNAs to HLA-G and Risk of Asthma

Cited by 347 publications

References 34 publications

Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F _2α Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese Population

Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F _2α Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese Population

MicroRNA-21 Is Up-Regulated in Allergic Airway Inflammation and Regulates IL-12p35 Expression

HLA-G genetic variants and hepatocellular carcinoma: a meta-analysis

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Allele-Specific Targeting of microRNAs to HLA-G and Risk of Asthma

Cited by 347 publications

References 34 publications

Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F 2α Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese Population

Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F 2α Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese Population

MicroRNA-21 Is Up-Regulated in Allergic Airway Inflammation and Regulates IL-12p35 Expression

HLA-G genetic variants and hepatocellular carcinoma: a meta-analysis

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Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F _2α Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese Population

Rare SNP rs12731181 in the miR-590-3p Target Site of the Prostaglandin F _2α Receptor Gene Confers Risk for Essential Hypertension in the Han Chinese Population