title: Alpha-1 antitrypsin Pi*Z gene frequency and Pi*ZZ genotype numbers worldwide: an update.
abstract: In alpha-1 antitrypsin deficiency (AATD), the Z allele is present in 98% of cases with severe disease, and knowledge of the frequency of this allele is essential from a public health perspective. However, there is a remarkable lack of epidemiological data on AATD worldwide, and many of the data currently used are outdated. Therefore, the objective of this study was to update the knowledge of the frequency of the Z allele to achieve accurate estimates of the prevalence and number of Pi*ZZ genotypes worldwide based on studies performed according to the following criteria: 1) samples representative of the general population, 2) AAT phenotyping characterized by adequate methods, and 3) measurements performed using a coefficient of variation calculated from the sample size and 95% confidence intervals. Studies fulfilling these criteria were used to develop maps with an inverse distance weighted (IDW)-interpolation method, providing numerical and graphical information of Pi*Z distribution worldwide. A total of 224 cohorts from 65 countries were included in the study. With the data provided by these cohorts, a total of 253,404 Pi*ZZ were estimated worldwide: 119,594 in Europe, 91,490 in America and Caribbean, 3,824 in Africa, 32,154 in Asia, 4,126 in Australia, and 2,216 in New Zealand. In addition, the IDW-interpolation maps predicted Pi*Z frequencies throughout the world even in some areas that lack real data. In conclusion, the inclusion of new well-designed studies and the exclusion of the low-quality ones have significantly improved the reliability of results, which may be useful to plan strategies for future research and diagnosis and to rationalize the therapeutic resources available.
authors.affiliation: Alpha1-Antitrypsin Deficiency Spanish Registry (REDAAT), Fundación Respira, Spanish Society of Pneumology and Thoracic Surgery (SEPAR), Barcelona.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Blanco
authors.affiliation: Internal Medicine Department, County Hospital of Jarrio.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bueno
authors.affiliation: Materials and Energy Department, School of Mining Engineering, Oviedo University.
authors.forename: Isidro
authors.initials: I
authors.lastname: Diego
authors.affiliation: Surgical Department, University Central Hospital of Asturias (HUCA), Oviedo, Principality of Asturias.
authors.forename: Sergio
authors.initials: S
authors.lastname: Pérez-Holanda
authors.affiliation: Pneumology Department, Complejo Hospitalario Universitario de Granada, Granada.
authors.forename: Francisco
authors.initials: F
authors.lastname: Casas-Maldonado
authors.affiliation: Pneumology Department, Hospital Universitari Vall d'Hebron.
authors.forename: Cristina
authors.initials: C
authors.lastname: Esquinas
authors.affiliation: Pneumology Department, Hospital Universitari Vall d'Hebron; CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Miravitlles
mesh_terms: D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D014943:Global Health; D006801:Humans; D008957:Models, Genetic; D017720:Molecular Epidemiology; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000175:diagnosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*
chemical_list: C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin
keywords: SERPINA1; alpha-1 antitrypsin deficiency; genetic epidemiology; geographic information system; inverse distance weighted interpolation; protease inhibitor