Background: Severe alpha-1-antitrypsin (ATT) deficiency is an inherited disorder associated with a high risk of developing pulmonary emphysema and several liver diseases. Over 90 different variants of gene which expresses AAT have been described. The commonest defective variants are Z and S. Determination of gene frequencies of abnormal variants is important to estimate the number of subjects at risk of suffering from diseases related with severe AAT deficiency in any given population.
Population and methods: In randomly selected general population, we determined the Pi phenotype to 1,116 subjects enrolled in the municipal population register from the high and middle Nalon basins. Mean age of the collective (male, 45%; female, 55%) was 46.2 (SD 29.9) years (range 4-91). AAT serum levels were determined by immunonephelometry. Pi phenotypes were determined by isoelectrofocusing in polyacrilamide gel.
Results: The phenotypes found were: PiMM, 857 subjects (22.5%); PiMS, 202 (18.1%); PiMZ, 31 (2.8%); PiSZ, 13 (1.2%); PiZZ, 0 (0.0%); PiMF, 5 (0.4%); Piss, 4 (0.4%); PiMN, 2 (0.2%); PiMB, 1 (0.08%); and PiMV, 1 (0.08%). The allelic frequencies were: PiM, 87.6%; PiS, 9.99%; PiZ, 1.97%; PiF, 0.2%; PiN, 0.09%; PiB, = 0.04%, and PiV, 0.04%. Therefore, the ZZ homozygote prevalence is 1 in 2,557, according to the Hardy-Weinberg principle. AAT serum levels (mg/dl) were: PiMM 147.7 (29.9) (89-296); PiMS 123.8 (22.5) (range 76-222); PiMZ 93.9 (18) (60-146); PiSS 107.5 (14.5) (87-121) and PiSZ 71.2 (12.6) (55-94).
Conclusions: The frequency of Z allele in the analyzed population (19.7 per 1000) is one of the highest in Europe, and in the world. The allelic frequency of S allele (99.9 per 1000) is similar to others found in several regions in the Iberian Peninsula.