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Alpha1-antitrypsin: Physiology, genetics and pathology

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Summary

Alpha1-antitrypsin (α1) is a glycoprotein in human serum that inhibits the enzymatic activity of trypsin and other proteolytic enzymes. Its concentration in normal serum is 200–250 mg/100 ml. In certain physiological and pathological situations, such as pregnancy, under contraceptive medication and during inflammation, the level of α1-at is elevated. The physiological role of α1 is not known, but the interaction with proteolytic enzymes from white blood cells is probably important. Electrophoretic techniques distinguish several phenotypes, which can be explained by the existence of several codominant alleles at one locus (probably the structural locus). Two alleles PiZ and PiS cause low concentrations of α1-at in serum: the approximate concentrations of α1-at for the different phenotypes are Z/Z 10%, M/Z 50–60%, S/S 60%, M/S 80%, where the level of 212 mg/100 ml found in the M/M phenotype is taken as 100%; thus the effect of these alleles on the α1-at concentration is additive. Homozygosity for the PiZ allele is strongly associated with chronic obstructive lung disease and there is also an association of COPD and heterozygosity for the PiZ or PiS or both, but to a lesser degree.

Zusammenfassung

α1-Antitrypsin (α1-at) ist ein Glykoprotein des menschlichen Serums. Es hemmt die enzymatische Aktivität von Trypsin und anderen proteolytischen Enzymen. Die Konzentration in normalem Serum beträgt etwa 200–250 mg/100 ml. Unter bestimmten physiologischen und pathologischen Bedingungen, z. B. während der Schwangerschaft, nach Verabreichung von Ovulationshemmern und während einer Infektion, ist der Serumspiegel des α1-at erhöht. Die genaue physiologische Funktion des α1-at ist unbekannt, wahrscheinlich ist aber die Hemmung von proteolytischen Enzymen aus Leukocyten von Bedeutung. Mit Hilfe elektrophoretischer Methoden kann man einige Phänotypen unterscheiden. Diese Phänotypen können durch mehrere codominante Allele an einem Locus, wahrscheinlich dem Strukturlocus, erklärt werden. Zwei Allele, PiZ und PiS, verursachen niedrige Konzentrationen von α1 im Serum: Die ungefähren Serumkonzentrationen von α1-at der verschiedenen Phänotypen sind: Z/Z 10%, M/Z 50–60%, S/S 60%, M/S 80%; die Konzentration von 212 mg/100 ml des M/M-Phänotyps ist hier gleich 100% gesetzt. Die Wirkung der verschiedenen Allele auf die α1-at ist also additiv. Homozygotie für das PiZ-Allel ist statistisch signifikant mit chronisch obstruktivem Lungenemphysem assoziiert. Eine geringere, aber ebenfalls statistisch signifikante Assoziation mit chronisch obstruktivem Lungenemphysem besteht auch für die Heterozygotie PiM/PiZ und PiM/PiS oder nur für eine von beiden Heterozygotien.

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    F. Kueppers

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Kueppers, F. Alpha1-antitrypsin: Physiology, genetics and pathology. Hum Genet 11, 177–189 (1971). https://doi.org/10.1007/BF00274738

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