Allelic frequencies of alpha-1-antitrypsin gene in randomly selected general population from an area of Asturias (Cantabrian coast, north of Spain)

BACKGROUND: Severe alpha-1-antitrypsin (ATT) deficiency is an inherited dis order associated whith a high risk of developing pulmonary emphysema and se veral liver diseases. Over 90 different variants of gene which expresses AA T have been described. The commonest defective variants are Z and S. Determ ination of gene frequencies of abnormal variants is important to estimate t he number of subjects at risk of suffering from diseases related with sever e AAT deficiency in any given population. POPULATION AND METHODS: In randomly selected general population. we determi ned 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%); Pi SS, 4 (0.4%); PIMN, 2 (0,2%); PiMB, 1 (0.08%); and PiMV, 1 (0.08%). The all elic 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 prevalenc e is 1 in 2,557, according to the Hardy-Weinberg principle. AAT serum level s (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 frequ ency of S allele (99.9 per 1000) is similar to others found in several regi ons in the Iberian Peninsula.