title: Heterozygosity of alpha 1-antitrypsin: a health risk?
abstract: alpha 1-Antitrypsin is a serum glycoprotein synthesized in the liver. It consists of a single polypeptide chain with a molecular weight of about 52,000. The molecule exhibits great genetic diversity with multiple codominant alleles at a single autosomal locus. The majority of the population expresses the M allele. The Z allele, which is the result of a single amino acid substitution, results in levels of alpha 1-antitrypsin that are only 10 to 15% of normal when inherited in the homozygous state. Two main pathological consequences of this state are liver and lung disease. The homozygous S phenotype has also been associated with reduced alpha 1-antitrypsin levels and pathology. The homozygous Z phenotype has an incidence of about 1 in 1700 in certain European populations. People who are heterozygous for the S or Z allele usually have alpha 1-antitrypsin levels which are about 60% of normal. The combined frequency of these alleles in the population may reach 10 to 15%. This review examines the controversy as to whether these individuals are at increased risk for pathology due to their reduced alpha 1-antitrypsin levels.
authors.affiliation: Department of Pathology, University of Iowa, Iowa City.
authors.forename: R D
authors.initials: RD
authors.lastname: Feld
mesh_terms: D001327:Autoimmune Diseases / Q000209:etiology; D004198:Disease Susceptibility; D006580:Genetic Carrier Screening / Q000379:methods; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008107:Liver Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D012307:Risk Factors; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency
chemical_list: D000515:alpha 1-Antitrypsin