Am. J. Respir. Crit. Care Med.,
Volume 159, Number 5, May 1999, 1624-1628
1-Antitrypsin Genotypes and the Acute-phase
Response to Open Heart Surgery
ANDREW J.
SANDFORD,
TABASSUM
CHAGANI,
JOHN J.
SPINELLI,
and
PETER D.
PARÉ
University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver; Department of Health Care
and Epidemiology, University of British Columbia, Vancouver; and Health Research Centre, St. Paul's Hospital, Vancouver,
British Columbia, Canada
A mutation in the 3' region of the 
1-antitrypsin (1-AT) gene is associated with chronic obstructive
pulmonary disease (COPD). However, the reason for this association is unknown. The mutation does
not cause 1-AT deficiency but in vitro studies suggest it could attenuate the rise in 1-AT levels during the acute-phase response. Therefore, we sought an association between the 3' mutation and a reduced rise in 1-AT levels following open heart surgery, a known trigger of the acute-phase response.
We genotyped 198 patients and identified 31 with the 3' mutation. Their 1-AT rise was compared
with the remaining 167 wild type subjects. Multiple linear regression analysis identified sex, urgency
of surgery, and surgical pump time as significant independent predictors of the rise in 1-AT. However, we found no association between the 3' mutation and a reduced rise in 1-AT. We also identified patients who had the Z and S 1-AT deficiency mutations and found a significant reduction in the
rise in 1-AT in individuals who were heterozygous for the Z mutation compared with wild type subjects. However, when the rise in 1-AT was expressed as a percentage of the basal level, there was no
significant difference between individuals who had the S or Z mutations compared with wild type.
Therefore, an attenuated 1-AT acute-phase response does not explain previous associations of the 3'
and S mutations with COPD. However, a deficient acute-phase rise in 1-AT may contribute to the
susceptibility to COPD associated with the Z mutation.
