IFRD1 modulates disease severity in cystic fibrosis through the regulation of neutrophil effector function

Ehrnhoefer, DE

doi:10.1111/j.1399-0004.2009.01247_2.x

Cited by 8 publications

(16 citation statements)

References 9 publications

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“…Analysis of the correlation between IFRD1 polymorphism rs7817 and nasal polyposis in CF patients. (18) . Hector et al (29) observed an up-regulation of IFRD1 expression in human CF neutrophils and found it linked to reactive oxygen species (ROS) production.…”

Section: Discussionmentioning

confidence: 99%

“…The change from a cytosine to a tymine in the rs7817 polymorphism occurs in the 3' UTR region of the IFRD1 gene (30) . The rs7817 SNP contains a target site for microRNA-577 (miR-577), expressed mainly in neutrophils, and a predicted site for splice enhancement (16,18) . Presently, there is no evidence whether this SNP could alter gene expression or whether the microRNA could alter the protein level.…”

Section: Discussionmentioning

confidence: 99%

“…Few studies reported the role of the Interferon-Related Developmental Regulator 1 (IFRD1, OMIM#603502) gene (7q22-q31) as a possible modifier of CF lung disease severity though the regulation of the neutrophil effector function (16)(17)(18) . IFRD1 mediates the transcriptional activity of NFκB p65 in neutrophils becoming a key player in the inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

“…Three Single Nucleotide Polymorphisms (SNPs) (rs6968084, rs3807213, rs7817) have been described in association with more severe lung phenotypes in CF patients (16) . These SNPs contain predicted binding sites for microRNAs as well as predicted splice enhancer sites, and could thereby modify this flogistic mechanism (18) . In this study, these three SNPs are analyzed to investigate a possible association with the development of NP in patients with CF.…”

Section: Introductionmentioning

confidence: 99%

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IFRD1 gene polymorphisms are associated with nasal polyposis in cystic fibrosis patients

Baldan¹,

Ar²,

Belpinati³

et al. 2015

Rhin

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

IFRD1 gene polymorphisms are associated with nasal polyposis in cystic fibrosis patients

Baldan¹,

Ar²,

Belpinati³

et al. 2015

Rhin

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show abstract

“…Previous studies found high expression in human blood cells (SymAtlas, 2008) and Gu et al found highest expression in neutrophils, where up-regulation occurs during the final differentiation steps (Ehrnhoefer, 2009; Gu et al, 2009). The authors suggested that IFRD1 modulates CF lung disease through the regulation of neutrophil effector function, but that other explanations, involving different cell types, should not be ignored.…”

Section: Associating Genes and Insight Into Their Modifying Mechanismsmentioning

confidence: 93%

Genetic Influences on Cystic Fibrosis Lung Disease Severity

Weiler¹,

Drumm²

2013

Front. Pharmacol.

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Understanding the causes of variation in clinical manifestations of disease should allow for design of new or improved therapeutic strategies to treat the disease. If variation is caused by genetic differences between individuals, identifying the genes involved should present therapeutic targets, either in the proteins encoded by those genes or the pathways in which they function. The technology to identify and genotype the millions of variants present in the human genome has evolved rapidly over the past two decades. Originally only a small number of polymorphisms in a small number of subjects could be studied realistically, but speed and scope have increased nearly as dramatically as cost has decreased, making it feasible to determine genotypes of hundreds of thousands of polymorphisms in thousands of subjects. The use of such genetic technology has been applied to cystic fibrosis (CF) to identify genetic variation that alters the outcome of this single gene disorder. Candidate gene strategies to identify these variants, referred to as “modifier genes,” has yielded several genes that act in pathways known to be important in CF and for these the clinical implications are relatively clear. More recently, whole-genome surveys that probe hundreds of thousands of variants have been carried out and have identified genes and chromosomal regions for which a role in CF is not at all clear. Identification of these genes is exciting, as it provides the possibility for new areas of therapeutic development.

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Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes

Chen

Tsai

Wang

et al. 2021

Sci Rep

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We hypothesized that epigenetics is a link between smoking/allergen exposures and the development of Asthma and chronic obstructive pulmonary disease (ACO). A total of 75 of 228 COPD patients were identified as ACO, which was independently associated with increased exacerbations. Microarray analysis identified 404 differentially methylated loci (DML) in ACO patients, and 6575 DML in those with rapid lung function decline in a discovery cohort. In the validation cohort, ACO patients had hypermethylated PDE9A (+ 30,088)/ZNF323 (− 296), and hypomethylated SEPT8 (− 47) genes as compared with either pure COPD patients or healthy non-smokers. Hypermethylated TIGIT (− 173) gene and hypomethylated CYSLTR1 (+ 348)/CCDC88C (+ 125,722)/ADORA2B (+ 1339) were associated with severe airflow limitation, while hypomethylated IFRD1 (− 515) gene with frequent exacerbation in all the COPD patients. Hypermethylated ZNF323 (− 296) / MPV17L (+ 194) and hypomethylated PTPRN2 (+ 10,000) genes were associated with rapid lung function decline. In vitro cigarette smoke extract and ovalbumin concurrent exposure resulted in specific DNA methylation changes of the MPV17L / ZNF323 genes, while 5-aza-2′-deoxycytidine treatment reversed promoter hypermethylation-mediated MPV17L under-expression accompanied with reduced apoptosis and decreased generation of reactive oxygen species. Aberrant DNA methylations may constitute a determinant for ACO, and provide a biomarker of airflow limitation, exacerbation, and lung function decline.

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IFRD1 modulates disease severity in cystic fibrosis through the regulation of neutrophil effector function

Abstract: Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease Gu et al. (2009) Nature 458: 1039–1044

Cited by 8 publications

References 9 publications

IFRD1 gene polymorphisms are associated with nasal polyposis in cystic fibrosis patients

IFRD1 gene polymorphisms are associated with nasal polyposis in cystic fibrosis patients

Genetic Influences on Cystic Fibrosis Lung Disease Severity

Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes

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