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      Alpha-1 antitrypsin Pi*SZ genotype: estimated prevalence and number of SZ subjects worldwide

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          The alpha-1 antitrypsin (AAT) haplotype Pi*S, when inherited along with the Pi*Z haplotype to form a Pi*SZ genotype, can be associated with pulmonary emphysema in regular smokers, and less frequently with liver disease, panniculitis, and systemic vasculitis in a small percentage of people, but this connection is less well established. Since the detection of cases can allow the application of preventive measures in patients and relatives with this congenital disorder, the objective of this study was to update the prevalence of the SZ genotype to achieve accurate estimates of the number of Pi*SZ subjects 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) selection of studies with reliable results assessed with a coefficient of variation calculated from the sample size and 95% confidence intervals. Studies fulfilling these criteria were used to develop tables and maps with an inverse distance-weighted (IDW) interpolation method, to provide numerical and geographical information of the Pi*SZ distribution worldwide. A total of 262 cohorts from 71 countries were included in the analysis. With the data provided by these cohorts, a total of 1,490,816 Pi*SZ were estimated: 708,792 in Europe; 582,984 in America and Caribbean; 85,925 in Africa; 77,940 in Asia; and 35,176 in Australia and New Zealand. Remarkably, the IDW interpolation maps predicted the Pi*SZ prevalence throughout the entire world even in areas lacking real data. These results may be useful to plan strategies for future research, diagnosis, and management of affected individuals.

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          Most cited references 40

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          An adaptive inverse-distance weighting spatial interpolation technique

           George Lu,  David Wong (2008)
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            Liver disease in alpha1-antitrypsin deficiency detected by screening of 200,000 infants.

             T Sveger (1976)
            We prosepctively studied 200,000 newborns to determine the frequency and clinical characteristics of alpha1-antitrypsin deficiency. One hundred and twenty Pi Z, 48 Pi SZ, two PI Z-and one Pi S-infants were identified and followed to the age of six months. Fourteen of 120 Pi Z infants had prolonged obstructive jaundice, nine with severe clinical and laboratory evidence of liver disease. Five had only laboratory evidence of liver disease. Eight other Pi Z infants had minimal abnormalities in serum bilirubin and hepatic enzyme activity and variable hepatosplenomegaly. All 22 Pi Z infants with hepatic abnormalities, two thirds of whom were made, appeared healthy at six months of age. Ninety-eight Pi Z infants did not have clinical liver disease, but liver-function tests gave abnormal results in 44 of 84 at three months, and in 36 of 60 at six months of age. The number of small-for-gestational-age infants was greater (P less than 0.001) among those with clinical liver disease. None of the 48 Pi SZ infants had clinical liver disease, but 10 of 42 at three months and one of 22 at six months of age had abnormal liver function. The Pi Z and Pi SZ phenotypes are associated with covert or readily apparent hepatic dysfunction in the first three months of life.
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              Molecular basis of alpha-1-antitrypsin deficiency.

              Alpha-1-antitrypsin (A1AT) deficiency is an autosomal hereditary disorder associated with a major reduction in serum A1AT levels. Clinically, A1AT deficiency is associated with emphysema in adults and, less commonly, liver disease in neonates. A1AT is a 52-kDa, 394-amino acid, single-chain glycoprotein normally present in serum at 150 to 350 mg/dl. The A1AT gene, composed of seven exons dispersed over 12 kb of chromosomal segment 14q31-32.3, is expressed in hepatocytes and mononuclear phagocytes. The A1AT protein, a member of the class of protease inhibitor proteins known as serpins (serine protease inhibitors), is a globular molecule composed of nine alpha-helices and three beta-pleated sheets. The major function of A1AT is to inhibit neutrophil elastase; A1AT does so through an active site centered around Met358 contained within an external stressed loop on the surface of the molecule. A1AT is a highly pleomorphic protein with greater than 75 variants determined at the protein and/or gene level. These variants can be categorized into four groups according to their serum A1AT level and function: normal, deficient, dysfunctional, and absent. There are two important salt bridges within the A1AT molecule (Glu342-Lys290; Glu263-Lys387); a mutation in the A1AT gene causing disruption of either salt bridge causes distinct molecular pathology resulting in reduced serum A1AT levels. Clinically relevant variants can be distinguished by a combination of isoelectric focusing of serum, restriction fragment length analysis of genomic DNA, oligonucleotide probes, and direct sequencing of the variant A1AT genes.

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                08 June 2017
                : 12
                : 1683-1694
                [1 ]Alpha1-Antitrypsin Deficiency Spanish Registry (REDAAT), Lung Foundation Breathe, Spanish Society of Pneumology (SEPAR), Barcelona, Spain
                [2 ]Internal Medicine Department, County Hospital of Jarrio, Principality of Asturias, Spain
                [3 ]Materials and Energy Department, School of Mining Engineering, Oviedo University, Principality of Asturias, Spain
                [4 ]Surgical Department, University Central Hospital of Asturias, Oviedo, Spain
                [5 ]Respiratory Medicine Department, Coventry and Warwickshire University Hospital, Coventry, UK
                [6 ]Pneumology Department, University Hospital San Cecilio, Granada, Spain
                [7 ]Pneumology Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain
                [8 ]CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain
                Author notes
                Correspondence: Marc Miravitlles, Pneumology Department, Hospital Universitari Vall d’Hebron, Passeig de la Vall d’Hebron 119-129, 08035 Barcelona, Spain, Tel +34 93 274 6107, Email mmiravitlles@
                © 2017 Blanco et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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