title: The G/G genotype of transforming growth factor beta 1 (TGF-beta1) single nucleotide (+915G/C) polymorphism coincident with other host and environmental factors is associated with irreversible bronchoconstriction in asthmatics.
abstract: Irreversible airflow obstruction may develop in some cases of asthma even in absence of known risk factors such as smoking and environmental insults and despite implementing apparently appropriate therapy. This implies that genetic factors may significantly contribute to determining the severity in the course of the disease. The published reports on genetic predisposition to irreversible bronchoconstriction in asthma, however, are relatively scarce, and disregard its potential association with transforming growth factor (TGF)-beta1 gene polymorphism despite established role that TGF-beta1 plays in airway remodelling. We tested TGF-beta1 single-nucleotide polymorphisms (SNPs) at position +869 of codon 10 (leucine or proline) and position +915 of codon 25 (arginine or proline) for association with irreversible bronchoconstriction in a case-control study involving 110 patients with asthma and 109 controls. Multivariate logistic regression analysis revealed that genotype G/G at codon 25 was significantly associated with irreversible bronchoconstriction in asthmatics (odds ratio = 4.44; 95% confidence interval: 1.00-19.61; P = 0.05), but only after adjustment for gender, disease duration and smoking index. The influence of SNPs at codon 10 on irreversible airway obstruction was not significant. Our results suggest that presence of SNP (+915G/G) at codon 25 in TGF-beta1 gene may predispose to the development of irreversible bronchoconstriction in asthmatic patients, but only when coincident with the male gender, habitual smoking and relevant duration of the disease.
authors.affiliation: Department of Internal Medicine and Allergology, Wroclaw Medical University, Wroclaw, Poland. Jerzy.Liebhart@dilnet.wroc.pl
authors.forename: Jerzy
authors.initials: J
authors.lastname: Liebhart
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Polak
authors.forename: Andrzej
authors.initials: A
authors.lastname: Dabrowski
authors.forename: Rafal
authors.initials: R
authors.lastname: Dobek
authors.forename: Ewa
authors.initials: E
authors.lastname: Liebhart
authors.forename: Anna
authors.initials: A
authors.lastname: Dor-Wojnarowska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Barg
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kulczak
authors.forename: Wojciech
authors.initials: W
authors.lastname: Medrala
authors.forename: Urszula
authors.initials: U
authors.lastname: Gladysz
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lange
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics*; D016084:Bronchoconstriction / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D003251:Constriction, Pathologic / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D053773:Transforming Growth Factor beta1