S and Z alpha1-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 asthma or bronchial hyperresponsiveness (BHR). This study deals with the effect 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 alpha1-antitrypsin levels were determined 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, i.e. SZ, SS and ZZ. Among the farmers, a significant positive trend for sensitization towards house dust mites was found, ranging from 12% in the MM group to 22% in the rare 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% for these symptoms among smokers in the rare Pi-group. On multiple logistic regression analysis, an increased odds ratio (OR) for BHR was found among farming school attendants with the rare Pi-alleles. The OR (95% confidence interval) was 1.71 (0.84-3.49) for MS, 1.93 (1.10-3.39) for MZ and 4.34 (1.19-15.8) 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 the farming occupation and the rare Pi-alleles, leading to a higher proportion of bronchial hyperresponsiveness related to the rare Pi-alleles in farming school attendants, in contrast to what is found among other young people living in rural areas.
Sigsgaard
T
T
Institute of Environmental and Occupational Medicine, Aarhus University, Denmark.
Brandslund
I
I
Omland
O
O
Hjort
C
C
Lund
E D
ED
Pedersen
O F
OF
Miller
M R
MR
D000328:Adult; D000382:Agricultural Workers' Diseases / Q000175:diagnosis / Q000235:genetics*; D000483:Alleles; D001249:Asthma / Q000175:diagnosis / Q000209:etiology; D016535:Bronchial Hyperreactivity / Q000175:diagnosis / Q000235:genetics*; D001985:Bronchial Provocation Tests; D016001:Confidence Intervals; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000175:diagnosis; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D012044:Regression Analysis; D012307:Risk Factors; D012882:Skin Tests; D013147:Spirometry; D000515:alpha 1-Antitrypsin / Q000235:genetics*
D000515:alpha 1-Antitrypsin