Alpha-1 antitrypsin deficiency in Italy: regional differences of the PIS and PIZ deficiency alleles

Background. Critical to the effective diagnosis and management of disease is information on its prevalence in a particular geographic area such as Italy. Alpha-1- antitrypsin deficiency (AAT Deficiency) is one of the most common serious hereditary diseases in the world, but its prevalence varies markedly from one country to another. AAT Deficiency affects at least 120.5 million carriers and deficient subjects worldwide for the two most prevalent deficiency alleles PIS and PIZ. This genetic disease is known to exist in Italy and is related to a high risk for development of jaundice in infants, liver disease in children and adults, and pulmonary emphysema in adults. Methods. Studies on the genetic epidemiology of AAT Deficiency has resulted in the development of a unique database that permits a unique analysis of the geographic distribution in 14 different regions located at random from Piemonte to Sicilia. Results. The use of Hardy-Weinberg statistical analysis to evaluate the distribution of these two deficiency alleles has demonstrated striking differences in the frequencies of these two deficiency alleles in these 14 different regions with 23/84 pair wise combinations significantly different (P=0.05) for PIS, and 5/84 combinations for PIZ. Conclusions. These findings demonstrate differences that impact the standards of care and diagnosis of AAT Deficiency in Italy since the prevalence of these deficiency alleles is not uniform throughout the country.