Estimated Prevalence and Number of PiMZ Genotypes of Alpha-1 Antitrypsin in Seventy-Four Countries Worldwide

Abstract

Background The α-1 antitrypsin (AAT) protease inhibitor PiMZ is a moderately deficient genotype, until recently considered of little or negligible risk. However, a growing number of studies show that MZ carriers have an increased risk of developing lung and liver diseases, if exposed to smoking or other airborne or industrial pollutants, and hepatotoxic substances. Methods We used the epidemiological studies performed to determine the frequencies of PiM and PiZ worldwide, based on the following criteria: 1) samples representative of the general population; 2) AAT phenotyping or genotyping characterized by adequate methods, including isoelectric focusing and polymerase chain reaction; and 3) studies with reliable results assessed with a coefficient of variation calculated from the sample size and 95% confidence intervals, to measure the precision of the results in terms of dispersion of the data around the mean. Results The present review reveals an impressive number of MZs of more than 35 million in 74 countries of the world with available data. Seventy-five percent of them are people of Caucasian European heritage, mostly living in Europe, America, Australia and New Zealand. Twenty percent of the remaining MZs live in Asia, with the highest concentrations in the Middle East, Eastern¸ Southern, and South-eastern regions of the Asian continent. The remaining five percent are Africans residing in Western and Eastern Africa. Conclusion Considering the high rate of smoking, the outdoor and the indoor air pollution from solid fuels used in cooking and heating, and the exposure to industrial dusts and chemicals in many of these countries, these figures are very worrying, and hence the importance of adequately assessing MZ subjects, recommending them rigorous preventive measures based on the adoption of healthy lifestyles, including avoidance of smoking and alcohol.

Liver disease progression in patients with alpha‐1 antitrypsin deficiency and protease inhibitor ZZ genotype with or without lung disease

“…In clinical practice, 96% of AATD‐related diseases occur in individuals with a homozygous Pi*ZZ genotype 4,5 . Other disease‐causing variants have a lower associated risk of severe disease, such as the heterozygous Pi*MZ genotype, which is estimated to occur in 2%–4% of the population with European ancestry 6 . Although a smaller proportion of patients with the Pi*MZ genotype experience AATD‐related diseases than those with the Pi*ZZ genotype, the higher prevalence of the Pi*MZ genotype in the population suggests that it could still be a significant public health concern 6,7 .…”

“…4,5 Other disease-causing variants have a lower associated risk of severe disease, such as the heterozygous Pi*MZ genotype, which is estimated to occur in 2%-4% of the population with European ancestry. 6 Although a smaller proportion of patients with the Pi*MZ genotype experience AATD-related diseases than those with the Pi*ZZ genotype, the higher prevalence of the Pi*MZ genotype in the population suggests that it could still be a significant public health concern. 6,7 Worldwide, it is estimated that 190 million people carry at least one of the S or Z SERPINA1 alleles associated with AATD, with about 5.5 million carrying two of these alleles (Pi*SS, Pi*SZ or Pi*ZZ).…”

“…6 Although a smaller proportion of patients with the Pi*MZ genotype experience AATD-related diseases than those with the Pi*ZZ genotype, the higher prevalence of the Pi*MZ genotype in the population suggests that it could still be a significant public health concern. 6,7 Worldwide, it is estimated that 190 million people carry at least one of the S or Z SERPINA1 alleles associated with AATD, with about 5.5 million carrying two of these alleles (Pi*SS, Pi*SZ or Pi*ZZ). 5 More than 250,000 individuals have AATD and the Pi*ZZ genotype.…”

Atteinte pulmonaire du déficit en alpha-1 antitrypsine. Recommandations pratiques pour le diagnostic et la prise en charge

“…Le DAAT est une des maladies génétiques autosomiques récessives les plus fréquentes avec une prévalence similaire à celle de la mucoviscidose [8]. Il a été estimé que dans le monde 250000 personnes seraient homozygotes ZZ [9] et plus de 35 millions seraient hétérozygotes [10]. Le DAAT prédomine chez les personnes d'origine européenne.…”

Disease Status at Diagnosis in Danish Children with α1‐antitrypsin Deficiency

“…M denotes the normal allele. Only ZZ-individuals are regarded as having AATD although SS-and MZ-individuals have reduced serum α 1 -antitrypsin (S-AAT) concentrations and increased risks of developing emphysema and end-stage liver disease (2)(3)(4). MS-individuals have not been found to have an increased risk of disease (4).…”