Genetic polymorphisms of xenobiotic-metabolizing enzymes influence the risk of pulmonary emphysema.

2.50
Hdl Handle:
http://hdl.handle.net/10146/199951
Title:
Genetic polymorphisms of xenobiotic-metabolizing enzymes influence the risk of pulmonary emphysema.
Authors:
Kukkonen, Mari K.; Hamalainen, Satu; Kaleva, Simo; Vehmas, Tapio; Huuskonen, Matti S.; Oksa, Panu; Vainio, Harri; Piirila, Paivi; Hirvonen, Ari
Abstract:
Pulmonary emphysema is a smoking-induced condition of the lung. Genetically determined differences in the activities of enzymes that metabolize oxidative agents are suspected to modify individual susceptibility to emphysema, as well as other smoking-related pulmonary disorders.; We investigated whether polymorphisms in selected xenobiotic-metabolizing enzyme genes predispose to emphysematous changes and airflow limitation among Finnish Caucasian construction workers.; PCR-based methods were used to analyze nine common polymorphisms in EPHX1, GSTM1, GSTM3, GSTP1, GSTT1, and NAT2 genes among 988 Finnish construction workers. The genotype data were compared with different emphysematous signs confirmed with high-resolution computed tomography and with forced vital capacity and forced expiratory volume in 1 s. For this, linear and logistic regression analyses, adjusted for the potential confounders, were used.; The EPHX1 Tyr113His polymorphism was associated with emphysematous changes (P=0.007), including paraceptal (P=0.039), panlobular (P=0.013), and bullae (P=0.003) type changes. The GSTM3 promoter polymorphism was associated with forced expiratory volume in 1 s/forced vital capacity ratio (P=0.010), and the GSTT1 genotype with emphysematous signs (P=0.008), including paraceptal (P=0.015), panlobular (P=0.031), and bullae-type (P=0.045) changes. In further analysis, the GSTT1 deletion was found to pose a two-fold overall risk for having emphysematous changes (odds ratio: 2.01; 95% confidence interval: 1.33-3.03), and almost a four-fold risk for having severe emphysematous changes (odds ratio: 3.70; 95% confidence interval: 2.15-6.36).; The results indicate a significant modifying role for GSTT1 gene polymorphism in the individual risk and severity of emphysematous changes.
Citation:
Pharmacogenet. Genomics 2011, 21 (12):876-883
Journal:
Pharmacogenetics and Genomics
Issue Date:
Dec-2011
URI:
http://hdl.handle.net/10146/199951
DOI:
10.1097/FPC.0b013e32834d597f
PubMed ID:
22027651
Additional Links:
http://journals.lww.com/jpharmacogenetics/pages/articleviewer.aspx?year=2011&issue=12000&article=00012&type=abstract
Type:
Article
Language:
en
ISSN:
1744-6880
Sponsors:
This study was financially supported by the Finnish Work Environment Fund (Grant 105091) and ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: ‘Food Quality and Safety’ (Contract No 513943).
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorKukkonen, Mari K.en
dc.contributor.authorHamalainen, Satuen
dc.contributor.authorKaleva, Simoen
dc.contributor.authorVehmas, Tapioen
dc.contributor.authorHuuskonen, Matti S.en
dc.contributor.authorOksa, Panuen
dc.contributor.authorVainio, Harrien
dc.contributor.authorPiirila, Paivien
dc.contributor.authorHirvonen, Arien
dc.date.accessioned2012-01-04T10:26:18Z-
dc.date.available2012-01-04T10:26:18Z-
dc.date.issued2011-12-
dc.identifier.citationPharmacogenet. Genomics 2011, 21 (12):876-883en
dc.identifier.issn1744-6880-
dc.identifier.pmid22027651-
dc.identifier.doi10.1097/FPC.0b013e32834d597f-
dc.identifier.urihttp://hdl.handle.net/10146/199951-
dc.description.abstractPulmonary emphysema is a smoking-induced condition of the lung. Genetically determined differences in the activities of enzymes that metabolize oxidative agents are suspected to modify individual susceptibility to emphysema, as well as other smoking-related pulmonary disorders.en
dc.description.abstractWe investigated whether polymorphisms in selected xenobiotic-metabolizing enzyme genes predispose to emphysematous changes and airflow limitation among Finnish Caucasian construction workers.en
dc.description.abstractPCR-based methods were used to analyze nine common polymorphisms in EPHX1, GSTM1, GSTM3, GSTP1, GSTT1, and NAT2 genes among 988 Finnish construction workers. The genotype data were compared with different emphysematous signs confirmed with high-resolution computed tomography and with forced vital capacity and forced expiratory volume in 1 s. For this, linear and logistic regression analyses, adjusted for the potential confounders, were used.en
dc.description.abstractThe EPHX1 Tyr113His polymorphism was associated with emphysematous changes (P=0.007), including paraceptal (P=0.039), panlobular (P=0.013), and bullae (P=0.003) type changes. The GSTM3 promoter polymorphism was associated with forced expiratory volume in 1 s/forced vital capacity ratio (P=0.010), and the GSTT1 genotype with emphysematous signs (P=0.008), including paraceptal (P=0.015), panlobular (P=0.031), and bullae-type (P=0.045) changes. In further analysis, the GSTT1 deletion was found to pose a two-fold overall risk for having emphysematous changes (odds ratio: 2.01; 95% confidence interval: 1.33-3.03), and almost a four-fold risk for having severe emphysematous changes (odds ratio: 3.70; 95% confidence interval: 2.15-6.36).en
dc.description.abstractThe results indicate a significant modifying role for GSTT1 gene polymorphism in the individual risk and severity of emphysematous changes.en
dc.description.sponsorshipThis study was financially supported by the Finnish Work Environment Fund (Grant 105091) and ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: ‘Food Quality and Safety’ (Contract No 513943).-
dc.language.isoenen
dc.relation.urlhttp://journals.lww.com/jpharmacogenetics/pages/articleviewer.aspx?year=2011&issue=12000&article=00012&type=abstracten
dc.subjectPulmonary emphysemaen
dc.subjectSmokingen
dc.subjectGenotypeen
dc.subjectPolymorphismsen
dc.subjectSusceptibilityen
dc.subjectEnzymesen
dc.subject.meshArylamine N-Acetyltransferaseen
dc.subject.meshEpoxide Hydrolasesen
dc.subject.meshFemaleen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGenotypeen
dc.subject.meshGlutathione S-Transferase pien
dc.subject.meshGlutathione Transferaseen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshPolymorphism, Geneticen
dc.subject.meshPulmonary Emphysemaen
dc.subject.meshRisk Factorsen
dc.titleGenetic polymorphisms of xenobiotic-metabolizing enzymes influence the risk of pulmonary emphysema.en
dc.typeArticleen
dc.identifier.journalPharmacogenetics and Genomicsen

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