S and Z alpha(1)-antitrypsin alleles are risk factors for bronchial hyperresponsiveness in young farmers: an example of gene/environment interaction

Several studies have found an association between the rare Pi-alleles and a sthma or bronchial hyperresponsiveness (BHR), This study deals with the eff ect of Pi-type on BHR among 2,308 young Danish people living in rural areas with a mean+/-SD age of 19.7+/-2.4 yrs, Interviews, pulmonary function testing, bronchial histamine provocation and skin-prick tests were performed. Serum alpha(1)-antitrypsin levels were de termined and phenotyping was performed by means of isoelectric focusing and the subjects categorized into four groups: 1) MM and MX; 2) MS; 3) MZ; and 4) rare, ie. SZ, SS and ZZ, Among the farmers, a significant positive trend for sensitization towards h ouse dust mites was found, ranging from 12% in the MM group to 22% in the r are Pi-group. A positive test for trend was found within the Pi-groups in a one-sided test for doctor-diagnosed asthma with a peak prevalence of 40% f or these symptoms among smokers in the rare Pi-group. On multiple logistic regression analysis, an increased odds ratio (OR) for BHR was found among f arming school attendants with the rare Pi-alleles, The OR (95% confidence i nterval) was 1.71 (0.84-3.49) for MS, 1.93 (1.10-3.39) for MZ and 4.34 (1.1 9-15.8) for the rare Pi-group. Such a relationship was not found among the conscripts, These results show that a gene/environment interaction may exist between th e farming occupation and the rare Pi-alleles, leading to a higher proportio n of bronchial hyperresponsiveness related to the rare Pi-alleles in farmin g school attendants, in contrast to what is found among other young people living in rural areas.