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

Abstract

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.

Clinical considerations in individuals with α1-antitrypsin PI*SZ genotype

“…AATD is classically considered to be the PI*ZZ genotype; however, recent genetic prevalence data suggest the number of individuals worldwide with the PI*SZ genotype could be as much as 10 times more than those with the PI*ZZ genotype [13], and that almost half of the estimated 1.5 million people with the PI*SZ genotype live in Europe [13,14]. Therefore, the number of individuals with the PI*SZ genotype may be higher than previously thought.…”

The important role of primary care providers in the detection of alpha-1 antitrypsin deficiency

“…From approximately 100 genetic variants described [20], the most common mutant SERPINA1 alleles associated with disease are the 'S' and 'Z' alleles, and all together, combinations of the M, S, and Z alleles comprise the AAT genotypes of 96-98% of the world population [21]. The Z allele is the most frequent mutation associated with severe AAT deficiency, while the S allele confers only mild deficiency [22,23]. As shown in Table 1, median AAT concentrations in individuals with different genotypes vary, with individuals who are homozygous for the Z allele (PiZZ) or null mutations having the lowest serum AAT concentrations [11,24,25].…”

Diagnosis and treatment of lung disease associated with alpha one‐antitrypsin deficiency: A position statement from the Thoracic Society of Australia and New Zealand*

“…The frequency of the PiZ allele is reduced in most Asian populations and may be increased in Māori compared to New Zealand Europeans . The less severely deficient PiS allele frequency is estimated to be 44 and 39 per 1000 in Australia and New Zealand, respectively …”

“…7 The less severely deficient PiS allele frequency is estimated to be 44 and 39 per 1000 in Australia and New Zealand, respectively. 8 It is estimated that there are in excess of 30 000 individuals across Australia and New Zealand with AATD. 9,10 Many remain undiagnosed either because of a lack of clinical manifestation of their deficiency or through being unrecognized by their treating physicians.…”