BACKGROUND: Alpha-1-antitiypsin (A-1-AT) is an important protease inhibitor which provides approx. 90 % of the serum anti-protease activity. The majority of the population (∼ 90%) have the MM genotype (codominant inheritance). Classic A-1-AT deficiency occurs with the ZZ genotype and is rare. There are reports postulating that heterozygotes are at increased risk for pancreatitis; other authors have been unable to find such an association. AIM: This study was undertaken to prospectively evaluate the correlation of A-1-AT phenotypes and abnormal pancreatograms. Eiectrophoretic phenotypes correlate with genotypes. METHODS: A-1-AT phenotypes were determined by a reference laboratory in 333 consecutive patients undergoing ERCP for various indications. Pancreatograms were obtained in all and interpreted by experienced physicians without knowledge of the phenotyping results. The pancreatograms were classified for the purposes of this analysis as either normal or abnormal. Using the z-statistic it was estimated that a sample size of approx. 200 pts would be sufficient to detect a difference of 10% in the incidence of abnormal phenotypes (a=0.05 two-tailed, β=0.20). RESULTS: Number of Number of Phenotype Heterozygotes (%) Homozygotes * (%) MS 19 (5.7%) MZ 7 (2.1%) GM 3 (0.9%) Other 7 (2.1%) Total 36 (10.8%) 297 (89.2%) * M, MM1, M1M2, MM2-phenotypes Phenotype Pancreatogram Heterozygote Homozygote % Heterozygotes Normal 20 173 10.4% Abnormal 16 124 11.4% N.S. CONCLUSION: This large prospective study shows no significant difference in the prevalence of abnormal A-1-AT phenotypes (heterozygotes) in patients with normal (10.4%) and abnormal pancreatograms (11.4%). This would indicate that the heterozygote state plays no significant role in the pathogenesis of chronic pancreatitis.
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging