Genetic-environmental interactions in chronic airways obstruction

To examine patterns of interaction between cigarette smoking and genetic factors in relation to airways obstruction, cross sectional data were analysed on 1787 white non-patient adult participants in a genetic-epidemiological study of airways obstruction (AO), defined as one-second forced expiratory volume FEV1 less than 68% of forced vital capacity FVC. Interaction was examined between smoking and each of four factors previously found to be related to AO: alpha-1 antitrypsin (PiZ allele), ABO blood groups (A antigen), ABH non-secretor status, and first degree relationship to a COPD or lung cancer patient. Multiple linear regression was used to test for interaction and adjust mean FEV1 (as a per cent of FVC) and prevalence of AO for age, sex, socioeconomic status, coffee and alcohol intake. Statistical interaction was observed between smoking (measured in pack-years) and two genetic factors (presence of blood A antigen and the family history). At higher pack-year levels, those individuals with the A antigen or the family history, but especially those with both factors had a much lower mean FEV1/FVC % and a much higher prevalence of AO than expected based on a simple additive model. On the other hand, there was no interaction between smoking and PiZ allele, or smoking and ABH secretor status. The findings suggest a possible biological interaction between cigarette smoke and the airways of individuals with blood group A antigen and familial lung disease. The findings also emphasize the role of genetic-environmental interactions in chronic diseases of multifactorial aetiology.