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Published ahead of print on July 22, 2004, doi:10.1165/rcmb.2004-0027OC

Am. J. Respir. Cell Mol. Biol., Volume 31, Number 5, November 2004, 559-564

A more recent version of this article appeared on November 1, 2004
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Submitted on March 26, 2004
Revised on July 20, 2004

Alpha-1-antitrypsin as a risk for infant and adult respiratory outcomes in a national birth cohort

Michael E.J. Wadsworth1*, Lynne E Vinall2, Abigail L Jones3, Rebecca J Hardy1, David B Whitehouse3, Suzanne L Butterworth1, Warren S Hilder1, Jennifer U Lovegrove3, and Dallas M Swallow1

1 Department of Epidemiology and Public Health, MRC National Survey of Health and Development, London, United Kingdom, 2 Department of Epidemiology and Public Health, MRC National Survey of Health and Development, London, United Kingdom; Department of Biology, University College London, Galton Laboratory, London, United Kingdom, 3 Department of Biology, University College London, Galton Laboratory, London, United Kingdom

* To whom correspondence should be addressed. E-mail: m.wadsworth{at}ucl.ac.uk.

Reduced Alpha-1-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 years. We used data on a British national representative sample (n=5362), studied since birth in 1946 to age 53 years (when n=3035), 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 OR 2.32 (95% CI 1.37,3.92: S but not Z carriers OR 1.58 95%CI 1.10,2.28) after adjustment for environmental, socio-economic and developmental factors, and breast-feeding. There was no difference in the adult outcomes at 53 years according to genotype, nor was there any association of genotype with change in FEV1 between 43 and 53 year. Lower AAT, 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.




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