Polymer Formation in Patients with Alpha-1-Antitrypsin Deficiency, Comparison of Pi*ZZ, SZ and other Rare Allele Variants

<bold>Introduction:</bold> Patients with AATD have different phenotypes in pulmonary and hepatic disease. A correlation between liver dysfunction and polymer formation has been found in Pi*ZZ individuals, but no data are available for individuals with rare allele variants. <bold>Methods:</bold> Patients with AATD Pi*ZZ, SZ and rare allele variants were analyzed. In addition to clinical history, pulmonary and hepatic function tests, molecular characterization was performed, including measuring polymerization of the purified AAT protein. <bold>Results:</bold> 24 patients, 9 men and 15 women, age of 63.6±10.4 years, with FEV1 1.8±0.8, and 59.2±21.8% were examined. The genotype distribution was: 13 Pi*ZZ, 3 Pi*SZ and 8 rare allelic variants (Pi*Q0Heidelberg I (c.1072C > T), III (c.10del), IV (c.-5+1G > A and c.-472G > A), Pi*P-Lowell/P-Lowell, two times Pi*Z/P-Lowell, Pi*Z/MProcida and Pi*Q0Clayton/Q0Granite falls). 58.3% of the patients underwent augmentation therapy. Different degrees of polymerization were observed in the AAT isolated from the patients. The rare allele variants had the lowest polymer concentration (µg/ml) of 23.9/20.4/14.1/64.9/102.7/16.5/10.4 mean 36.1±34.7 followed by the Pi*SZ individuals 140.6±148.6, the highest values were found in the Pi*ZZ individuals 159.6±92.4, p=0.011. For the liver values GOT, GPT and gGT as well as the liver fibroscan, there were no differences between Pi*ZZ and individuals with rare genotypes, the latter with 6.9±2.6 and 6.4±3.1 kPa p=ns respectively. <bold>Conclusion:</bold> This study was the first to examine polymer formation in patients with rare AATD variants, the relationship between lung and liver function and polymers in this population needs further evaluation.