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Article: Complex two-gene modulation of lung disease severity in children with cystic fibrosis

TitleComplex two-gene modulation of lung disease severity in children with cystic fibrosis
Authors
Issue Date2008
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal Of Clinical Investigation, 2008, v. 118 n. 3, p. 1040-1049 How to Cite?
AbstractAlthough cystic fibrosis (CF) is a monogenic disease, its clinical manifestations are influenced in a complex manner. Severity of lung disease, the main cause of mortality among CF patients, is likely modulated by several genes. The mannose-binding lectin 2 (MBL2) gene encodes an innate immune response protein and has been implicated as a pulmonary modifier in CF. However, reports have been conflicting, and interactions with other modifiers have not been investigated. We therefore evaluated the association of MBL2 with CF pulmonary phenotype in a cohort of 1,019 Canadian pediatric CF patients. MBL2 genotypes were combined into low-, intermediate-, and high-expression groups based on MBL2 levels in plasma. Analysis of age at first infection with Pseudomonas aeruginosa demonstrated that MBL2 deficiency was significantly associated with earlier onset of infection. This MBL2 effect was amplified in patients with high-producing genotypes of transforming growth factor beta 1 (TGFB1). Similarly, MBL2 deficiency was associated with more rapid decline of pulmonary function, most significantly in those carrying the high-producing TGFB1 genotype. These findings provide evidence of gene-gene interaction in the pathogenesis of CF lung disease, whereby high TGF-β1 production enhances the modulatory effect of MBL2 on the age of first bacterial infection and the rate of decline of pulmonary function.
DescriptionComment in J Clin Invest. 2008 Mar;118(3):839-841
Persistent Identifierhttp://hdl.handle.net/10722/143107
ISSN
2014 Impact Factor: 13.215
2013 SCImago Journal Rankings: 9.511
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDorfman, Ren_HK
dc.contributor.authorSandford, Aen_HK
dc.contributor.authorTaylor, Cen_HK
dc.contributor.authorHuang, Ben_HK
dc.contributor.authorFrangolias, Den_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorSang, Ren_HK
dc.contributor.authorPereira, Len_HK
dc.contributor.authorSun, Len_HK
dc.contributor.authorBerthiaume, Yen_HK
dc.contributor.authorTsui, LCen_HK
dc.contributor.authorParé, PDen_HK
dc.contributor.authorDurie, Pen_HK
dc.contributor.authorCorey, Men_HK
dc.contributor.authorZielenski, Jen_HK
dc.date.accessioned2011-10-31T06:32:22Z-
dc.date.available2011-10-31T06:32:22Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Clinical Investigation, 2008, v. 118 n. 3, p. 1040-1049en_HK
dc.identifier.issn0021-9738en_HK
dc.identifier.urihttp://hdl.handle.net/10722/143107-
dc.descriptionComment in J Clin Invest. 2008 Mar;118(3):839-841-
dc.description.abstractAlthough cystic fibrosis (CF) is a monogenic disease, its clinical manifestations are influenced in a complex manner. Severity of lung disease, the main cause of mortality among CF patients, is likely modulated by several genes. The mannose-binding lectin 2 (MBL2) gene encodes an innate immune response protein and has been implicated as a pulmonary modifier in CF. However, reports have been conflicting, and interactions with other modifiers have not been investigated. We therefore evaluated the association of MBL2 with CF pulmonary phenotype in a cohort of 1,019 Canadian pediatric CF patients. MBL2 genotypes were combined into low-, intermediate-, and high-expression groups based on MBL2 levels in plasma. Analysis of age at first infection with Pseudomonas aeruginosa demonstrated that MBL2 deficiency was significantly associated with earlier onset of infection. This MBL2 effect was amplified in patients with high-producing genotypes of transforming growth factor beta 1 (TGFB1). Similarly, MBL2 deficiency was associated with more rapid decline of pulmonary function, most significantly in those carrying the high-producing TGFB1 genotype. These findings provide evidence of gene-gene interaction in the pathogenesis of CF lung disease, whereby high TGF-β1 production enhances the modulatory effect of MBL2 on the age of first bacterial infection and the rate of decline of pulmonary function.en_HK
dc.languageeng-
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.orgen_HK
dc.relation.ispartofJournal of Clinical Investigationen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCystic Fibrosis - genetics - physiopathology-
dc.subject.meshLung - physiopathology-
dc.subject.meshMannose-Binding Lectin - blood - genetics-
dc.subject.meshPseudomonas Infections - etiology-
dc.subject.meshTransforming Growth Factor beta1 - genetics-
dc.titleComplex two-gene modulation of lung disease severity in children with cystic fibrosisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9738&volume=118&issue=3&spage=1040&epage=1049&date=2008&atitle=Complex+two-gene+modulation+of+lung+disease+severity+in+children+with+cystic+fibrosis-
dc.identifier.emailTsui, LC: tsuilc@hkucc.hku.hken_HK
dc.identifier.authorityTsui, LC=rp00058en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1172/JCI33754en_HK
dc.identifier.pmid18292811en_HK
dc.identifier.pmcidPMC2248329-
dc.identifier.scopuseid_2-s2.0-40549083327en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-40549083327&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume118en_HK
dc.identifier.issue3en_HK
dc.identifier.spage1040en_HK
dc.identifier.epage1049en_HK
dc.identifier.isiWOS:000253646400028-
dc.publisher.placeUnited Statesen_HK
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dc.identifier.scopusauthoridDorfman, R=8934686800en_HK
dc.identifier.scopusauthoridSandford, A=7006552245en_HK
dc.identifier.scopusauthoridTaylor, C=7404823047en_HK
dc.identifier.scopusauthoridHuang, B=23973037100en_HK
dc.identifier.scopusauthoridFrangolias, D=55409585700en_HK
dc.identifier.scopusauthoridWang, Y=35076768800en_HK
dc.identifier.scopusauthoridSang, R=23973622500en_HK
dc.identifier.scopusauthoridPereira, L=7201962440en_HK
dc.identifier.scopusauthoridSun, L=8601648400en_HK
dc.identifier.scopusauthoridBerthiaume, Y=7003488718en_HK
dc.identifier.scopusauthoridTsui, LC=7102754167en_HK
dc.identifier.scopusauthoridParé, PD=7103044327en_HK
dc.identifier.scopusauthoridDurie, P=7005360997en_HK
dc.identifier.scopusauthoridCorey, M=7005819978en_HK
dc.identifier.scopusauthoridZielenski, J=7003732699en_HK

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