Alpha1-antitrypsin as a risk for infant and adult respiratory outcomes in a national birth cohort.
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.
Wadsworth
Michael E J
ME
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, United Kingdom. m.wadsworth@ucl.ac.uk
Vinall
Lynne E
LE
Jones
Abigail L
AL
Hardy
Rebecca J
RJ
Whitehouse
David B
DB
Butterworth
Suzanne L
SL
Hilder
Warren S
WS
Lovegrove
Jennifer U
JU
Swallow
Dallas M
DM
D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D004247:DNA / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D012141:Respiratory Tract Infections / Q000235:genetics / Q000378:metabolism; D012306:Risk; D013147:Spirometry; D013997:Time Factors; D000515:alpha 1-Antitrypsin / Q000235:genetics*
C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin; D004247:DNA