Age of SERPINA1 gene PI Z mutation: Swedish and Latvian population analysis

Alpha 1-antitrypsin (A1AT) deficiency, one of the most common inborn errors of metabolism in Caucasians, is characterized by a low serum concentration of A1AT and a high risk of pulmonary emphysema and liver disease. The allelic frequency for the most common protease inhibitor (PI) Z mutation in the SERPINA1 gene is 2-5% in Caucasians of European descent. The objective of our study was to estimate the PI Z mutation age using molecular analysis in Latvian and Swedish populations, which have the highest frequency of PI Z mutation. DNA samples of heterozygous and homozygous PI Z allele carriers from Latvia (n = 21) and Sweden (n = 65) were analysed; 113 unrelated healthy donors from Latvia were used as a control group. MALDI-TOF analysis was performed on all samples. Pairwise Fst was computed to compare the PI Z mutation ages between the two populations and controls. A p value less than 0.05 was considered significant. Analysis of non-recombinant SNPs revealed that the PI Z mutation age was 2902 years in Latvia (SD 1983) and 2362 years in Sweden (SD 1614) which correlates with previous studies based on microsatellite analysis.