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Alpha₁-Antitrypsin as a Risk for Infant and Adult Respiratory Outcomes in a National Birth Cohort

Medical Research Council National Survey of Health and Development, Department of Epidemiology and Public Health, Royal Free Hospital and University College London Medical School, London; and Galton Laboratory, Department of Biology, University College London, London, United Kingdom

Address correspondence to: Michael E. J. Wadsworth, Medical Research Council National Survey of Health and Development, Department of Epidemiology and Public Health, Royal Free Hospital and University College London Medical School, 1-19 Torrington Place, London WC1E 6BT, UK. E-mail: m.wadsworth{at}ucl.ac.uk

Reduced alpha₁-antitrypsin (AAT) encoded by the gene SERPINA1 is a potential risk for pulmonary disease. We investigated SERPINA1 polymorphism as a risk for infant and adult pulmonary morbidity, and adult respiratory function and its change between 43 and 53 yr. We used data on a British national representative sample (n = 5,362) studied since birth in 1946 to age 53 yr (when n = 3,035), when DNA was first obtained. SERPINA1 Z and, to a lesser extent, S carriers had an increased risk of infant lower respiratory infection compared with those who were neither S nor Z carriers (Z carriers: odds ratio = 2.32, 95% confidence interval = 1.37–3.92; S but not Z carriers odds ratio = 1.58, 95% confidence interval = 1.10–2.28) after adjustment for environmental, socioeconomic, and developmental factors, and breast-feeding. There was no difference in the adult outcomes at 53 yr according to genotype, nor was there any association of genotype with change in forced expiratory volume at 1 s between 43 and 53 yr. Lower alpha₁-antitrypsin, as indicated by carrier status for the Z and S alleles, was a risk for infant lower respiratory infection, but not for adult respiratory outcomes.

Abbreviations: alpha₁-antitrypsin, AAT • chronic obstructive pulmonary disease, COPD • forced expiratory volume at 1 s, FEV₁ • forced vital capacity, FVC • lower respiratory infection, LRI • Global Initiative for Chronic Obstructive Lung Disease, GOLD

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