alpha(1)-antitrypsin genotypes and the acute-phase response to open heart surgery

A mutation in the 3' region of the alpha(1)-antitrypsin (alpha(1)-AT) gene is associated with chronic obstructive pulmonary disease (COPD). However, t he reason for this association is unknown. The mutation does not cause alph a(1)-AT deficiency but in vitro studies suggest it could attenuate the rise in alpha(1)-AT levels during the acute-phase response. Therefore, we sough t an association between the 3' mutation and a reduced rise in alpha(1)-AT levels following open heart surgery, a known trigger of the acute-phase res ponse. We genotyped 198 patients and identified 31 with the 3' mutation. Th eir alpha(1)-AT rise was compared with the remaining 167 wild type subjects . Multiple linear regression analysis identified sex, urgency of surgery, a nd surgical pump time as significant independent predictors of the rise In alpha(1)-AT. However, we found no association between the 3' mutation and a reduced rise in alpha(1)-AT. We also identified patients who had the Z and S alpha(1)-AT deficiency mutations and found a significant reduction in th e rise in alpha(1)-AT in individuals who were heterozygous for the Z mutati on compared with wild type subjects. However, when the rise in alpha(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 w ild type. Therefore, an attenuated alpha(1)-AT acute-phase response does no t explain previous associations of the 3' and S mutations with COPD. Howeve r, a deficient acute-phase rise in alpha(1)-AT may contribute to the suscep tibility to COPD associated with the Z mutation.