Genetic epidemiology of Alpha-1 antitrypsin deficiency

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Introduction

The proteinase inhibitor (Pi*) Z allele is present in 98% of cases of alpha-1 antitrypsin (AAT) deficiency (AATD) with severe disease, and in clinical practice 96% of pathologies associated with AATD occur in homozygous Pi*ZZ, and the remaining 4% in heterozygous Pi*SZ and in the extremely infrequent "rare" and "null" genotypes.

Prevalence and number of Pi*ZZ genotypes worldwide

Europe

In Europe, the highest prevalence of Pi*ZZ genotypes (1 every 1,600–3,000 subjects) are found in southern Sweden and Norway, Denmark, Baltic Republics, Finland, Netherlands, Belgium, western of France, south of England, Ireland and in the Iberian Peninsula. In central Europe the prevalence is 1: 4,500–5,000, and gradually decreases towards the east, and in the most remote regions of the north and south of the continent, with 1: 10,000 in the Balkan Peninsula and 1: 90,000 in the European Russia. In round numbers, in Europe there may be at least 120,000 Pi*ZZ genotypes, most of them in Germany, France, the Iberian Peninsula, UK, Italy, Poland, Belgium, Netherlands and Northern Europe countries.

America and Caribbean

In North America, the prevalence of Pi*ZZ is 1: 5,000 in the north-east of Canada and the United States, and gradually decreases (1: 7,000) to the west, north and south-eastern of the continent. Prevalence falls very sharply in Mexico, Central America, and Caribbean and South America countries. There could be over 90,000 individuals carrying Pi*ZZ genotypes in North America, Central America, South America and Caribbean islands. Most of these ZZ individuals are in the US (approximately 70,000, 95% of them Caucasians). In addition, it has been estimated that there may be (in round numbers) 7,000 in Canada; 4,000 in Mexico; 6,000 in Brazil; around of 2,000 in Colombia, Venezuela and Argentina; 1,000 in Peru; 700 in Chile; 600 in Cuba, and lesser amounts in other American countries. Ref. 3 [Blanco I, Bueno P, Diego I, Pérez-Holanda S, Casas-Maldonado F, Esquinas C, Miravitlles M. (2017). Alpha-1 antitrypsin Pi*Z gene frequency and Pi*ZZ genotype numbers worldwide: an update. International Journal of Chronic Obstructive Pulmonary Disease 12:561–569.]

Africa and Asia

The Pi*ZZ genotype is practically absent throughout Asia, except in Pakistan and Thailand, which show moderate values. According to this low prevalence, in Asia, with more than 4 billion people would have about of 30,000 Pi*ZZ, most of them in Pakistan, Thailand and South Korea. The ZZ genotype is very rare in Africa. Only in the Horn of Africa a low or moderate ZZ prevalence have been described, being very low or absent in the remainder African countries. Accordingly, it has been estimated that there may be around of 4,000 Pi*ZZ in more than 1.2 billion people from Africa, mainly distributed by Nigeria and Somalia.

Australia and New Zealand

In Australia and New Zealand Pi*ZZ prevalence is very similar to those found in the Republic of Ireland and United Kingdom (approx. 1: 2,000 – 5,000). In total, these countries would have about of 6,000 Pi*ZZ (4,000 in Australia and 2,000 in New Zealand), most of them descendants of Anglo Saxon settlers.

Blanco et al (2017) Alpha-1 antitrypsin Pi*Z gene frequency and Pi*ZZ genotype numbers worldwide: an update. International Journal of Chronic Obstructive Pulmonary Disease 12:561–569

Prevalence and number of Pi*SZ genotypes worldwide

Compound heterozygous SZ are relatively frequent in Caucasian subjects living in Europe, the American continent, Australia and New Zealand. According to the known data, it is estimated to be a total of 1,500,000 Pi*SZ genotypes in the countries where AATD has been studied. Of the approximately 1.5 million people with SZ genotype worldwide, 48% are in Europe; 39% in America (the majority in North America, Brazil, Venezuela and Colombia); the remaining 13% in white individuals residing in New Zealand and Australia, and in a small percentage of African and Asian subjects unevenly distributed throughout Africa, and western and southern Asia.

Blanco et al (2017) Alpha-1 antitrypsin Pi*SZ genotype: estimated prevalence and number of SZ subjects worldwide. International Journal of Chronic Obstructive Pulmonary Disease 12:1683–1694

References

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