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.
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
Michael E J
ME
Wadsworth
Lynne E
LE
Vinall
Abigail L
AL
Jones
Rebecca J
RJ
Hardy
David B
DB
Whitehouse
Suzanne L
SL
Butterworth
Warren S
WS
Hilder
Jennifer U
JU
Lovegrove
Dallas M
DM
Swallow
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