SERPINE1 -675 4G/5G polymorphism is associated with asthma severity and inhaled corticosteroid response

Dijkstra, Ate; Postma, Dirkje S.; Bruinenberg, Marcel; Diemen, Cleo C. van; Boezen, H. Marike; Koppelman, Gerard H.; Timens, Wim; Vonk, Judith M.

doi:10.1183/09031936.00182410

Cited by 27 publications

(24 citation statements)

References 61 publications

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“…After reading full texts of the remaining 20 articles, twelve were then excluded and eight remained. One article reported two cohorts [14], and each cohort was considered as a separate case-control study. Finally, a total of 9 case-control studies in 8 articles were identified met our inclusion criteria [7]–[14], including 1817 cases and 2327 controls.…”

Section: Resultsmentioning

confidence: 99%

“…One article reported two cohorts [14], and each cohort was considered as a separate case-control study. Finally, a total of 9 case-control studies in 8 articles were identified met our inclusion criteria [7]–[14], including 1817 cases and 2327 controls. There were 4 studies of Asians [9], [11]–[13] and 4 studies of Caucasians [7], [8], [10], [14].…”

Section: Resultsmentioning

confidence: 99%

“…Finally, a total of 9 case-control studies in 8 articles were identified met our inclusion criteria [7]–[14], including 1817 cases and 2327 controls. There were 4 studies of Asians [9], [11]–[13] and 4 studies of Caucasians [7], [8], [10], [14]. Four studies were performed in adults [10], [12]–[14], one in children [11], and three included both children and adults [7]–[9].…”

Section: Resultsmentioning

confidence: 99%

“…The 4G/5G polymorphism is a major genetic determinant of plasma PAI-1 levels [6] and has been studied as a potential susceptibility factor for asthma. Several studies reported the association between the 4G/5G polymorphism of PAI-1 gene and the risk of asthma [7]–[14], but the results were inconclusive.…”

Section: Introductionmentioning

confidence: 99%

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The −675 4G/5G Polymorphism in Plasminogen Activator Inhibitor-1 Gene Is Associated with Risk of Asthma: A Meta-Analysis

Nie

Li²,

Xiu

2012

PLoS ONE

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BackgroundA number of studies assessed the association of −675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility.MethodsDatabases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model.ResultsEight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12–2.18, P = 0.008), 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06–1.80, P = 0.02), 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17–2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07–1.84, P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08–1.68, P = 0.008).ConclusionsThis meta-analysis suggested that the −675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The −675 4G/5G Polymorphism in Plasminogen Activator Inhibitor-1 Gene Is Associated with Risk of Asthma: A Meta-Analysis

Nie

Li²,

Xiu

2012

PLoS ONE

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“…Maior frequência do alelo mutado (53%) foi encontrada em holandeses, e o genótipo 4G/4G estava presente em 28% da população (Dijkstra et al, 2011).…”

Section: Polimorfismo No Gene Do Pai-1 (Serpine1 4g/5g)unclassified

Polimorfismos genéticos relacionados à hemostasia e a sua relação com abortos espontâneos recorrentes

Bertinato¹

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CMTR1 is associated with increased asthma exacerbations in patients taking inhaled corticosteroids

Dahlin

Denny

Roden

et al. 2015

Immunity Inflam & Disease

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Inhaled corticosteroids (ICS) are the most effective controller medications for asthma, and variability in ICS response is associated with genetic variation. Despite ICS treatment, some patients with poor asthma control experience severe asthma exacerbations, defined as a hospitalization or emergency room visit. We hypothesized that some individuals may be at increased risk of asthma exacerbations, despite ICS use, due to genetic factors. A GWAS of 237,726 common, independent markers was conducted in 806 Caucasian asthmatic patients from two population‐based biobanks: BioVU, at Vanderbilt University Medical Center (VUMC) in Tennessee (369 patients), and Personalized Medicine Research Project (PMRP) at the Marshfield Clinic in Wisconsin (437 patients). Using a case–control study design, the association of each SNP locus with the outcome of asthma exacerbations (defined as asthma‐related emergency department visits or hospitalizations concurrent with oral corticosteroid use), was evaluated for each population by logistic regression analysis, adjusting for age, gender and the first four principal components. A meta‐analysis of the results was conducted. Validation of expression of selected candidate genes was determined by evaluating an independent microarray expression data set. Our study identified six novel SNPs associated with differential risk of asthma exacerbations (P < 10−05). The top GWAS result, rs2395672 in CMTR1, was associated with an increased risk of exacerbations in both populations (OR = 1.07, 95% CI 1.03–1.11; joint P = 2.3 × 10−06). Two SNPs (rs2395672 and rs279728) were associated with increased risk of exacerbations, while the remaining four SNPs (rs4271056, rs6467778, rs2691529, and rs9303988) were associated with decreased risk. Three SNPs (rs2395672, rs6467778, and rs2691529) were present in three genes: CMTR1, TRIM24 and MAGI2. The CMTR1 mRNA transcript was significantly differentially expressed in nasal lavage samples from asthmatics during acute exacerbations, suggesting potential involvement of this gene in the development of this phenotype. We show that genetic variability may contribute to asthma exacerbations in patients taking ICS. Furthermore, our studies implicate CMTR1 as a novel candidate gene with potential roles in the pathogenesis of asthma exacerbations.

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SERPINE1 -675 4G/5G polymorphism is associated with asthma severity and inhaled corticosteroid response

Cited by 27 publications

References 61 publications

The −675 4G/5G Polymorphism in Plasminogen Activator Inhibitor-1 Gene Is Associated with Risk of Asthma: A Meta-Analysis

The −675 4G/5G Polymorphism in Plasminogen Activator Inhibitor-1 Gene Is Associated with Risk of Asthma: A Meta-Analysis

Polimorfismos genéticos relacionados à hemostasia e a sua relação com abortos espontâneos recorrentes

CMTR1 is associated with increased asthma exacerbations in patients taking inhaled corticosteroids

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