Genetic association between obstructive bronchitis and enzymes of oxidative stress.
OBJECTIVE
Obstructive respiratory diseases, mainly the chronic obstructive pulmonary disease (COPD) and asthma, are associated with functional polymorphisms of xenobiotic-metabolizing enzymes (XMEs). To date, association for obstructive bronchitis has not been described.


METHODS
In this study, we investigated the genotypes from 26 functional polymorphisms of 20 XMEs in children (n, 1028) at the age of 6 years from the German prospective birth cohort study (LISAplus) and analyzed the associations between genotypes and obstructive bronchitis.


RESULTS
For the first time, we found noteworthy gene-disease associations for the functional PON1 M55L and EPHX1 H139R polymorphisms and gene-environment associations for the functional COMT V158M and NQO1 P187S polymorphisms after stratification for maternal active smoking behaviour during pregnancy. The noteworthy associations were substantiated by the biological findings that all the risk genotypes belong to genes involved in oxidative stress and code for proteins with a fast enzymatic activity or concomitantly appear in common estrogene-metabolizing pathway (COMT, NQO1).


CONCLUSIONS
The oxidative stress has to be taken into account in mechanism of the obstructive bronchitis in early childhood. The risk genotypes may serve as risk factors for respiratory obstruction rather than for signs of COPD or asthma.
UFZ-Helmholtz Centre for Environmental Research, Department of Environmental Immunology, Leipzig, Germany. mario.bauer@ufz.de
Mario
M
Bauer
Carolin
C
Gräbsch
Uwe
U
Schlink
Norman
N
Klopp
Thomas
T
Illig
Ursula
U
Krämer
Andrea
A
von Berg
Beate
B
Schaaf
Michael
M
Borte
Joachim
J
Heinrich
Olf
O
Herbarth
Irina
I
Lehmann
Stefan
S
Röder
D000328:Adult; D001120:Arginine; D043303:Aryldialkylphosphatase / Q000235:genetics*; D001991:Bronchitis / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D016009:Chi-Square Distribution; D002648:Child; D015331:Cohort Studies; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006639:Histidine; D006801:Humans; D007930:Leucine; D008173:Lung Diseases, Obstructive / Q000235:genetics*; D008297:Male; D008715:Methionine; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects; D011392:Proline; D011446:Prospective Studies; D012307:Risk Factors; D012694:Serine; D012907:Smoking / Q000009:adverse effects; D014633:Valine
D012694:Serine; D006639:Histidine; D001120:Arginine; D011392:Proline; D008715:Methionine; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D002394:Catechol O-Methyltransferase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human; D007930:Leucine; D014633:Valine