<scp>MUC</scp>5<scp>B</scp> promoter polymorphism in <scp>J</scp>apanese patients with idiopathic pulmonary fibrosis

Horimasu, Yasushi; Ohshimo, Shinichiro; Bonella, Francesco; Tanaka, Sonosuke; Ishikawa, Nobuhisa; Hattori, Noboru; Kohno, Nobuoki; Guzman, Josune; Costabel, Ulrich

doi:10.1111/resp.12466

Cited by 103 publications

(79 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5,7,8,10,14,22 Multiple separate studies have shown a strong association between IPF and the T minor allele. [6][7][8][9][10][11][12][13] The odds ratios for pulmonary fibrosis among subjects who were heterozygous and those who were homozygous for the T minor allele of this SNP were 9.0 (95% CI, 6.2-13.1) and 21.8 (95% CI, 5.1-93.5) in the original description. 5 Our results showed significant differences in the pattern of pulmonary fibrosis on CT scans relative to the rs35705950 SNP, with the T group showing a lower proportion of ground-glass opacity, higher proportion of subpleural distribution, and higher proportion of confident UIP diagnoses.…”

Section: Discussionmentioning

confidence: 93%

“…This is supported by the strong association between IPF and the MUC5B polymorphism in previous studies. [6][7][8][9][10][11][12][13] If this is true, this SNP would be an important marker in those at risk for pulmonary fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…This finding has been validated in multiple separate study cohorts. [6][7][8][9][10][11][12][13] Other studies failed to show an association between the MUC5B promoter polymorphism and other causes of pulmonary fibrosis, suggesting that it may be specific to IPF. 6,8,14 IPF is the most common subtype of the idiopathic interstitial pneumonias.…”

mentioning

confidence: 99%

See 2 more Smart Citations

CT Imaging Phenotypes of Pulmonary Fibrosis in the MUC5B Promoter Site Polymorphism

Chung

Peljto

Chawla

et al. 2016

Chest

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CT Imaging Phenotypes of Pulmonary Fibrosis in the MUC5B Promoter Site Polymorphism

Chung

Peljto

Chawla

et al. 2016

Chest

View full text Add to dashboard Cite

show abstract

“…Indeed, a single nucleotide polymorphism in TOLLIP, associated with mortality, was linked to reduced expression of TOLLIP, and recent post hoc analysis suggests that it affects the response to N-acetylcysteine [101,102,105,106].…”

Section: Non-mendelian Inheritance In Pulmonary Fibrosismentioning

confidence: 99%

Management of suspected monogenic lung fibrosis in a specialised centre

et al. 2017

View full text Add to dashboard Cite

At least 10% of patients with interstitial lung disease present monogenic lung fibrosis suspected on familial aggregation of pulmonary fibrosis, specific syndromes or early age of diagnosis. Approximately 25% of families have an identified mutation in genes mostly involved in telomere homeostasis, and more rarely in surfactant homeostasis.Beyond pathophysiological knowledge, detection of these mutations has practical consequence for patients. For instance, mutations involved in telomere homeostasis are associated with haematological complications after lung transplantation and may require adapted immunosuppression. Moreover, relatives may benefit from a clinical and genetic evaluation that should be specifically managed.The field of genetics of pulmonary fibrosis has made great progress in the last 10 years, raising specific problems that should be addressed by a specialised team.

show abstract

“…Among Asians, the MAF of rs35705950 is low, but in Japanese and Chinese studies, subjects with IPF had a significantly higher frequency of the risk allele than controls 13 17. The rs35705950 MAF across different ethnic groups appears to reflect disease prevalence in these groups, since NHWs have been observed to be at higher risk of pulmonary fibrosis than Hispanics, Asians and Africans 18.…”

Section: Muc5b Promoter Polymorphismmentioning

confidence: 92%

Pulmonary fibrosis in the era of stratified medicine

Mathai

Newton

Schwartz

et al. 2016

Thorax

View full text Add to dashboard Cite

Both common and rare variants contribute to the genetic architecture of pulmonary fibrosis. Genome-wide association studies have identified common variants, or those with a minor allele frequency of >5%, that are linked to pulmonary fibrosis. The most widely replicated variant (rs35705950) is located in the promoter region of the MUC5B gene and has been strongly associated with idiopathic pulmonary fibrosis (IPF) and familial interstitial pneumonia (FIP) across multiple different cohorts. However, many more common variants have been identified with disease risk and in aggregate account for approximately one-third of the risk of IPF. Moreover, several of these common variants appear to have prognostic potential. Next generation sequencing technologies have facilitated the identification of rare variants. Recent whole exome sequencing studies have linked pathogenic rare variants in multiple new genes to FIP. Compared with common variants, rare variants have lower population allele frequencies and higher effect sizes. Pulmonary fibrosis rare variants genes can be subdivided into two pathways: telomere maintenance and surfactant metabolism. Heterozygous rare variants in telomere-related genes co-segregate with adult-onset pulmonary fibrosis with incomplete penetrance, lead to reduced protein function, and are associated with short telomere lengths. Despite poor genotype-phenotype correlations, lung fibrosis associated with pathogenic rare variants in different telomere genes is progressive and displays similar survival characteristics. In contrast, many of the heterozygous rare variants in the surfactant genes predict a gain of toxic function from protein misfolding and increased endoplasmic reticulum (ER) stress. Evidence of both telomere shortening and increased ER stress have been found in sporadic IPF patients, suggesting that the mechanisms identified from rare variant genetic studies in unique individuals and families are applicable to a wider spectrum of patients. The ability to sequence large cohorts of individuals rapidly has the potential to further our understanding of the relative contributions of common and rare variants in the pathogenesis of pulmonary fibrosis. The UK 100,000 Genomes Project will provide opportunities to interrogate both common and rare variants and to investigate how these biological signals provide diagnostic and prognostic information in the era of stratified medicine.

show abstract

MUC5B promoter polymorphism in Japanese patients with idiopathic pulmonary fibrosis

Abstract: The association between rs35705950 and IPF was also present in this Japanese cohort, but was not as strong as the German counterpart. To our knowledge, this is the first study to successfully validate the association between rs35705950 and IPF in a Japanese ethnicity.

Cited by 103 publications

References 25 publications

CT Imaging Phenotypes of Pulmonary Fibrosis in the MUC5B Promoter Site Polymorphism

CT Imaging Phenotypes of Pulmonary Fibrosis in the MUC5B Promoter Site Polymorphism

Management of suspected monogenic lung fibrosis in a specialised centre

Pulmonary fibrosis in the era of stratified medicine

Contact Info

Product

Resources

About