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Bauer, M.* ; Gräbsch, C.* ; Schlink, U.* ; Klopp, N. ; Illig, T. ; Krämer, U.* ; von Berg, A.* ; Schaaf, B.* ; Borte, M.* ; Heinrich, J. ; Herbarth, O.* ; Lehmann, I.* ; Roder, S.*

Genetic association between obstructive bronchitis and enzymes of oxidative stress.

Metabolism 61, 1771-1779 (2012)

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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. Material/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 P1875 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). Conclusion. 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.

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