Interleukin 1 receptor antagonist polymorphisms are associated with the risk of developing acute coronary syndrome in Mexicans

Fragoso, José Manuel; Delgadillo, Hilda; Llórente, Luis; Chuquiure, Eduardo; Juárez‐Cedillo, Teresa; Vallejo, Maité; Lima, Guadalupe; Furuzawa‐Carballeda, Janette; Peña‐Duque, Marco Antonio; Martínez-Ríos, Marco Antonio; Vargas‐Alarcón, Gilberto

doi:10.1016/j.imlet.2010.08.003

Cited by 23 publications

(17 citation statements)

References 29 publications

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“…Furthermore, the levels of IL-1, a proinflammatory molecule, are higher in the brain stems of 22 wk old SHR compared with age-matched WKY (51). Additional human studies have also found that Il1rn has single nucleotide polymorphisms that contribute to acute coronary syndrome, which further implicates this gene in cardiovascular disease (19). In our results, Il1rn is expressed at higher levels in WKY than in SHR.…”

Section: Discussionsupporting

confidence: 82%

“…We focused on potential target genes that are involved processes with known functional impact on development and maintenance of hypertension. We developed a list of 144 potential target transcripts that are associated with AT1R signaling through Pkc, CamkII, Mapk, and Pi3k pathways, immediate early genes (e.g., Fos, Egr1, Egr2, Egr3, Jun, Junb), and ion channels and transporters, guided by our previous studies (27,34,39,40,42,51,53,54), as well as genes relevant to inflammatory pathways shown to affect blood pressure regulation, including interleukins, chemokines, and leukotrienes (19,52,60). Several of these pathways are enriched in astrocytes (e.g., inflammatory processes) compared with neurons (e.g., ion channels) compared with endothelial cells (e.g., junctional proteins), whereas the transcriptional regulators and signaling pathways may be common to all cell types (38).…”

Section: Resultsmentioning

confidence: 99%

“…We pursued a combination of approaches for microRNA/ mRNA target prediction, including use of miRWALK (18) database, RNA22 (35) tool for pattern matching, and literaturederived known functional interactions (19,51,56,59,61). Our results revealed that several of the hypertension-relevant functional processes could be targeted by the key differentially expressed microRNAs, yielding a putative microRNA/mRNA regulatory network (Supplemental Table S1).…”

Section: Resultsmentioning

confidence: 99%

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MicroRNA network changes in the brain stem underlie the development of hypertension

DeCicco

Zhu

Brureau

et al. 2015

Physiological Genomics

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sion is a major chronic disease whose molecular mechanisms remain poorly understood. We compared neuroanatomical patterns of microRNAs in the brain stem of the spontaneous hypertensive rat (SHR) to the Wistar Kyoto rat (WKY, control). We quantified 419 wellannotated microRNAs in the nucleus of the solitary tract (NTS) and rostral ventrolateral medulla (RVLM), from SHR and WKY rats, during three main stages of hypertension development. Changes in microRNA expression were stage-and region-dependent, with a majority of SHR vs. WKY differential expression occurring at the hypertension onset stage in NTS versus at the prehypertension stage in RVLM. Our analysis identified 24 microRNAs showing time-dependent differential expression in SHR compared with WKY in at least one brain region. We predicted potential gene regulatory targets corresponding to catecholaminergic processes, neuroinflammation, and neuromodulation using the miRWALK and RNA22 databases, and we tested those bioinformatics predictions using high-throughput quantitative PCR to evaluate correlations of differential expression between the microRNAs and their predicted gene targets. We found a novel regulatory network motif consisting of microRNAs likely downregulating a negative regulator of prohypertensive processes such as angiotensin II signaling and leukotriene-based inflammation. Our results provide new evidence on the dynamics of microRNA expression in the development of hypertension and predictions of microRNA-mediated regulatory networks playing a region-dependent role in potentially altering brain-stem cardiovascular control circuit function leading to the development of hypertension.hypertension; microRNA; neuroinflammation; angiotensin II; brain stem HYPERTENSION IS A MAJOR CHRONIC disease worldwide, affecting about 50 million adults in the United States alone. It is a multiorgan disease and a major cause of heart failure, coronary heart disease, atrial fibrillation, stroke, and end-stage renal disease, and it has an enormous economic impact. About 90 -95% of cases are "essential" with no known medical cause (11). Moreover, only about a third of hypertensive patients have their blood pressure fully controlled (11). A significant and increasing population (ϳ25%) of hypertensive patients is drug resistant. There remains an unmet need for antihypertensive therapy.In the context of the recent discovery of novel lines of therapeutic interventions involving approaches to modulate microRNA we decided to elucidate changes in microRNA levels during the development of spontaneous hypertensive rat (SHR) hypertension. The recent explosion in microRNA research has produced new computational and experimental approaches for studying microRNA functions in cell culture and in vivo, which we take advantage of here. MicroRNAs are an abundant class of small (ϳ22 nt) endogenous noncoding RNAs that direct posttranscriptional regulation of gene expression. There is ample evidence that dysregulation of microRNAs is associated with the pathogenesis of human diseases, in...

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Section: Discussionsupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA network changes in the brain stem underlie the development of hypertension

DeCicco

Zhu

Brureau

et al. 2015

Physiological Genomics

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“…Previous studies demonstrated that there is an association between the genotype of c/c IL-1RN and restenosis of the coronary artery after implantation bare metal stent, that is, a stent with an anti-inflammatory drug eluting stent. 15 Moreover, Fragoso et al 16 found that subjects who have polymorphism of IL-1RN6/2 gene are at risk of developing the acute coronary syndrome. This study shows that the risk of cardiovascular events is correlated with serum levels of IL-1RN in overweight subjects.…”

Section: Resultsmentioning

confidence: 99%

Assessment of serum interleukin-1receptor antagonist (IL-1RN) levels in overweight-obese women and its relation to the cardiovascular risk using Framingham score

Dezayee¹

2017

ZJMS

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“…With the rapid development of molecular biology technology, scientists have found many gene polymorphisms closely related to coronary heart disease susceptibility, such as those of angiotensin converting enzyme (Cambien et al, 1992;Narne et al, 2012), apolipoprotein (Hsu et al, 2006;Jang et al, 2009;Huang et al, 2012), cell factor (Zhong et al, 2009;Fragoso et al, 2010;Jin et al, 2012;Srikanth Babu et al, 2012), coagulation system (Pegoraro, 2005;Friso et al, 2012), and endothelin (Popov et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

MKL1-184C>T gene polymorphism is associated with coronary artery disease in the Chinese Han population

Bao

et al. 2014

Genet. Mol. Res.

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ABSTRACT. We investigated genetic susceptibility to coronary artery disease (CAD) by studying the association of MKL1 gene polymorphisms with CAD in the Chinese Han population. We performed a case-control study with 476 unrelated CAD patients and 325 non-CAD controls. All SNPs were genotyped with a TaqMan SNP genotyping assay. The distribution of MKL1-184C>T gene polymorphism in each group was in Hardy-Weinberg equilibrium. The frequency of the MKL1 T allele in the CAD group was significantly higher than in the control group (38.6 vs 30.8%). After logistic regression models adjusted for CAD risk factors, the risk of CAD among CT genotypes was 1.765 times higher than among the CC genotypes [odds ration (OR) = 1.765, 95% confidence interval (CI) = 1.246-2.5], and for TT genotypes it was 1.806 times higher than for the CC genotypes (OR = 1.806, 95%CI = 1.203-2.71). In summary, genotypes with at least one T allele (CT or TT genotypes) had a significantly increased CAD risk than the CC genotypes, with a ratio of 1.78 to 1 (OR = 1.780, 95%CI = 1.311-2.418). There was a close association between -184 T allele and 3VD (OR = 1.614, 95%CI = 1.259-2.07, P < 0.05). We conclude that the -184C>T of MKL1 is an important susceptibility factor for CAD in the Han Chinese in Henan Province. Homozygosity for the T allele is not only associated with an increased risk for CAD, it is also correlated with severity of stenosis in the Chinese Han population.

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Interleukin 1 receptor antagonist polymorphisms are associated with the risk of developing acute coronary syndrome in Mexicans

Cited by 23 publications

References 29 publications

MicroRNA network changes in the brain stem underlie the development of hypertension

MicroRNA network changes in the brain stem underlie the development of hypertension

Assessment of serum interleukin-1receptor antagonist (IL-1RN) levels in overweight-obese women and its relation to the cardiovascular risk using Framingham score

MKL1-184C>T gene polymorphism is associated with coronary artery disease in the Chinese Han population

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