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  • Title: Risk of hospital admission for obstructive pulmonary disease in alpha(1)-antitrypsin heterozygotes of phenotype PiMZ.
    Author: Seersholm N, Wilcke JT, Kok-Jensen A, Dirksen A.
    Journal: Am J Respir Crit Care Med; 2000 Jan; 161(1):81-4. PubMed ID: 10619801.
    Abstract:
    Whether subjects heterozygous for alpha(1)-antitrypsin (alpha(1)-AT) deficiency are at risk for development of obstructive pulmonary disease (OPD) has been discussed for the past three decades. Both cohort and case-control studies have reached different conclusions, with the major problems being small sample sizes. A cohort of heterozygotes with the phenotype PiMZ was retrieved from the Danish Alpha(1)-Antitrypsin Deficiency Registry. Ten matched controls for each PiMZ subject were identified from the files of the Danish Central Population Registry. Cases and controls were subsequently linked to the files of the Danish Hospital Discharge Registry, and relative risk for OPD was calculated. In the cohort of 1,551 PiMZ subjects (11,678 person-years), we identified 47 subjects with a discharge diagnosis of OPD, as compared with 206 subjects with this diagnosis in the control group (109,748 person-years), yielding a relative risk (RR) of 2.2 (95% confidence interval [CI]: 1.5 to 3.0). This increased risk was present in both men and women and in all age groups; however, it was significant only in the age group from 40 to 79 yr. Of the 1,551 PiMZ subjects, 565 (36%) were first-degree relatives of PiZ index cases, and it appeared that only this group was at increased risk of hospital admission for OPD (RR: 3.4, 95% CI: 2.2 to 5.3). We conclude that alpha(1)-AT heterozygotes of phenotype PiMZ are at increased risk of hospital admission for OPD if they are first-degree relatives of PiZ index cases only, and that other, yet unknown genetic or environmental factors contribute to the development of lung disease.
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