Antitrypsin genotype unaffected by age
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1 Department of Clinical Biochemistry, Herlev University Hospital, Copenhagen, Denmark; mdahl@partners.org
Keywords: 1-antitrypsin; age; genetics; 11; 47
In a recent otherwise excellent editorial in Thorax,1 Dr Seersholm indicated that our previous results on the decline in forced expiratory volume in 1 second (FEV1) based on the Copenhagen City Heart Study2 are biased. We disagree, and rather believe that our study of the general population is prone to less bias than case-control or family based studies.
Dr Seersholm argues that, because we genotyped study participants after measurement of FEV1 in 1976–8, 1981–4, and 1991–4, our results are biased.1 Certainly, if conventional risk factors are measured after development of disease, the disease might be the cause of the risk factor rather than vice versa. However, an 1-antitrypsin MZ genotype in a newborn does not change into a ZZ genotype by age. Therefore, the Pi MZ genotype preceded FEV1 outcomes in our study, even though genotypes were determined after FEV1 measurements. Using identical logic, the genotype preceded outcomes in a similar manner in other previous studies.3–6
Selection bias could potentially be a reason for discrepancies between studies on Pi MZ and COPD.1,7 In our study, where genotype distribution was in Hardy-Weinberg equilibrium, we found no evidence for selection against any 1-antitrypsin genotype.2,8 Therefore, as also pointed out by Dr Seersholm,1 selection bias is more likely in case-control and family based studies than in cohort studies of the general population.(M Dahl1 and B G Nordestga)
Keywords: 1-antitrypsin; age; genetics; 11; 47
In a recent otherwise excellent editorial in Thorax,1 Dr Seersholm indicated that our previous results on the decline in forced expiratory volume in 1 second (FEV1) based on the Copenhagen City Heart Study2 are biased. We disagree, and rather believe that our study of the general population is prone to less bias than case-control or family based studies.
Dr Seersholm argues that, because we genotyped study participants after measurement of FEV1 in 1976–8, 1981–4, and 1991–4, our results are biased.1 Certainly, if conventional risk factors are measured after development of disease, the disease might be the cause of the risk factor rather than vice versa. However, an 1-antitrypsin MZ genotype in a newborn does not change into a ZZ genotype by age. Therefore, the Pi MZ genotype preceded FEV1 outcomes in our study, even though genotypes were determined after FEV1 measurements. Using identical logic, the genotype preceded outcomes in a similar manner in other previous studies.3–6
Selection bias could potentially be a reason for discrepancies between studies on Pi MZ and COPD.1,7 In our study, where genotype distribution was in Hardy-Weinberg equilibrium, we found no evidence for selection against any 1-antitrypsin genotype.2,8 Therefore, as also pointed out by Dr Seersholm,1 selection bias is more likely in case-control and family based studies than in cohort studies of the general population.(M Dahl1 and B G Nordestga)