Chest
Volume 122, Issue 5, November 2002, Pages 1818-1829
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Special Reports
Worldwide Racial and Ethnic Distribution of α1-Antitrypsin Deficiency: Summary of an Analysis of Published Genetic Epidemiologic Surveys

https://doi.org/10.1378/chest.122.5.1818Get rights and content

Study objectives

α1-antitrypsin (AAT) deficiency is a genetic disease that is widely known in Europe as a disease of white individuals, who, along with their descendants in other parts of the world, are at the highest risk for liver and/or lung disease. There is a limited database of individuals affected by this disease worldwide. It has been estimated, for example, that there are 70,000 to 100,00 individuals affected in the United States, with comparable numbers in Europe.

Study design

Genetic epidemiologic studies in the peer-reviewed literature have been used in an exploratory study to estimate the number of carriers and the number of those individuals who are homozygous or heterozygous for the two most common defective alleles for AAT deficiency in 58 individual countries. The total country database of 373 control cohorts has been combined to estimate the numbers of carriers and deficiency allele combinations for PiS and PiZ in 11 geographic regions and worldwide. The study was designed to be illustrative rather than comprehensive, and more detailed publication of the enormous database developed in this exploratory study is planned.

Conclusions

The database presented indicates that in a total population of 4.4 billion in the countries surveyed worldwide, there are at least 116 million carriers (PiMS and PiMZ) and 3.4 million deficiency allele combinations (PiSS, PiSZ, and PiZZ). Furthermore, this database demonstrates that AAT deficiency is found in various populations of African blacks, Arabs and Jews in the Middle East, whites in Australia/New Zealand, Europe, and North America, central Asians, far east Asians, and southeast Asians. These data demonstrate that AAT deficiency is not just a disease of whites in Europe, but that it affects individuals in all racial subgroups worldwide. In addition, AAT deficiency may be one of the most common serious hereditary disorders in the world.

Section snippets

Source of Data

The articles used in the present analysis were obtained through a variety of sources such as searches of the peer-reviewed literature on PubMed and the Web of Science in the Library of the National Institutes of Health. In addition, articles on genetic epidemiologic surveys for AAT deficiency in Europe9 and for the Middle East14 also were used.

Selection of Cohorts

Only the data on the phenotypes of the control group cohort in each article were used in the present study. These control cohorts (ie, blood donors,

Estimation of the Numbers of Carriers and Deficiency Allele Combinations for PiS and PiZ in Africa

The database for 11 countries in central and southern Africa is given in Table 1. There are a total of 23 cohorts with a total cohort sample size of 3,886. The sample size of the different cohorts varies from 88 in Botswana to 1,354 in the Republic of South Africa. This tabulation demonstrates striking differences between the prevalence of carriers and deficiency allele combinations for PiS and PiZ within this part of the African continent. In the final tabulation, with an estimated population

Are the Carriers and Deficiency Allele Combinations for the PiS and PiZ at Risk for Adverse Health Effects?

The fact that carriers for various metabolic diseases as well as for AAT deficiency are at risk for adverse health effects has been well-documented.11 There are numerous metabolic diseases in which the carriers are at risk. These include disorders the expression of which is influenced by dietary factors as well as those that are independent of food intake.11

The issue for AAT deficiency is whether carriers for the two major defective alleles (ie, PiS and PiZ) are at risk. In his 1989 review, Feld

Summary and Conclusions

The major finding in the present study is that AAT deficiency affects all major racial subgroups worldwide. The data presented in Table 12 indicate that there are at least 116 million carriers (PiMS and PiMZ) and 3.4 million deficiency allele combinations (PiSS, PiSZ, and PiZZ) worldwide. Furthermore, this database demonstrates that AAT deficiency is found in African blacks, Arabs and Jews in the Middle East, whites worldwide, central Asians, far east Asians, and southeast Asians. We conclude

ACKNOWLEDGMENT

The author is indebted to Mr. Eric Steele of National Institute of Environmental Health Sciences contractor OAO Corporation (Greenbelt, MD) for help in the original design of the spreadsheets used in data processing. The author also is indebted to Drs. Ignacio Blanco and Enrique Bustillo for their help in the preparation of new spreadsheet templates with embedded formulas for Hardy-Weinberg equilibrium statistics and 95% confidence limits. The author also is indebted to Drs. Jack Lieberman,

References (40)

  • CA Blank et al.

    Clinical features and molecular characteristics of alpha 1-antitrypsin deficiency

    Ann Allergy

    (1994)
  • DW Cox et al.

    DNA restriction fragments associated with alpha 1-antitrypsin indicate a single origin for deficiency allele PI Z

    Nature

    (1985)
  • S Seixas et al.

    Patterns of haplotype diversity within the serpine gene cluster at 14q32.1: insights into the natural history of the alpha1-antitrypsin polymorphism

    Hum Genet

    (2001)
  • World Health Organization

    Alpha 1-Pi deficiency: World Health Organization

    Pneumologie

    (1997)
  • W Endres

    Inherited metabolic diseases affecting the carrier

    J Inherit Metab Dis

    (1997)
  • R Feld

    Heterozygosity of alpha-1-antitrypsin: a health risk?

    Crit Rev Clin Lab Sci

    (1989)
  • MF Gourley et al.

    Alpha 1-antitrypsin deficiency and the PiMS phenotype: case report and literature review

    J Pediatr Gastroenterol Nutr

    (1989)
  • S Nevo

    Protease inhibitor subtypes in some population groups from Israel

    Hum Hered

    (1987)
  • I Blanco et al.

    Alpha-1-antitrypsin PI phenotypes S and Z in Europe: an analysis of the published surveys

    Clin Genet

    (2001)
  • I Blanco et al.

    Distribution of alpha-1-antitrypsin PI S and PI Z frequencies in countries outside of Europe: a meta-analysis

    Clin Genet

    (2001)
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