alpha1-antitrypsin genotypes and the acute-phase response to open heart surgery

A mutation in the 3' region of the alpha1-antitrypsin (alpha1-AT) gene is associated with chronic obstructive pulmonary disease (COPD). However, the reason for this association is unknown. The mutation does not cause alpha1-AT deficiency but in vitro studies suggest it could attenuate the rise in alpha1-AT levels during the acute-phase response. Therefore, we sought an association between the 3' mutation and a reduced rise in alpha1-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 alpha1-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 alpha1-AT. However, we found no association between the 3' mutation and a reduced rise in alpha1-AT. We also identified patients who had the Z and S alpha1-AT deficiency mutations and found a significant reduction in the rise in alpha1-AT in individuals who were heterozygous for the Z mutation compared with wild type subjects. However, when the rise in alpha1-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 alpha1-AT acute-phase response does not explain previous associations of the 3' and S mutations with COPD. However, a deficient acute-phase rise in alpha1-AT may contribute to the susceptibility to COPD associated with the Z mutation.