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Pneumologie 2001; 55(7): 326-332
DOI: 10.1055/s-2001-15616
ORIGINALARBEIT
Georg Thieme Verlag Stuttgart · New York

Korrigierte Normwerte für das Serum-ACE durch Genotypisierung eines Deletions-/Insertions-Polymorphismus des ACE-Gens

Corrected normal values for serum ACE by genotyping the deletion-/insertion-polymorphism of the ACE geneB. Ruprecht1 , M. Schürmann2 , M. W. Ziegenhagen1 , E. vom Bauer3 , D. Meier4 , M. Schlaak1 , J. Müller-Quernheim1
  • 1Forschungszentrum Borstel, Medizinische Klinik(Leiter: Prof. Dr. P. Zabel)
  • 2Medizinische Universität Lübeck, Institut für Humangenetik (Leiter: Prof. Dr. E. Schwinger)
  • 3Gemeinschaftspraxis Dr. Kramer und Kollegen, Geesthacht
  • 4Bühlmann Laboratories AG, Schönenbuch (Schweiz)
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Publication History

Publication Date:
31 December 2001 (online)

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Zusammenfassung:

Hintergrund: Die Serum-Aktivität des angiotensinkonvertierenden Enzyms (ACE) gilt als wichtiger Aktivitätsparameter der Sarkoidose. Für das ACE-Gen ist seit 1990 ein Deletions-/Insertions-(D/I)Genpolymorphismus bekannt. Die Serum-ACE-Werte korrelieren mit dem Genotyp dieses Polymorphismus. Homozygote für die Deletion (DD) weisen die höchsten Werte auf, Homozygote für die Insertion (II) die niedrigsten, die Werte der Heterozygoten (DI) liegen dazwischen. Das Maß der Beeinflussung der ACE-Aktivität durch den Genpolymorphismus differiert in Populationen unterschiedlicher ethnischer Herkunft. Erstmals wurden anhand der Bestimmungen bei einem größeren Kollektiv gesunder Personen aus Norddeutschland genotypkorrigierte Normalbereiche für die hiesige Population erstellt.

Methodik: Bei 262 gesunden Personen wurde mittels einer PCR-Methodik aus genomischer DNA der Genotyp des ACE-D/I-Genpolymorphismus bestimmt und die ACE-Aktivität im Serum mittels eines kinetischen Tests gemessen.

Ergebnisse: Bei 29,4 % der untersuchten Personen liegt der Genotyp DD, bei 49,6 % DI und bei 21,0 % II vor. Eine vergleichbare Verteilung der Genotypen war auch in früheren Untersuchungen bei gesunden Mitteleuropäern gefunden worden. Die mittlere Serum-ACE-Aktivität (95 %-Konfidenzintervall) liegt beim Genotyp DD bei 59,8 U/l (31,8 - 87,8), beim Genotyp DI bei 47,7 U/l (18,6 - 76,8) und beim Genotyp II bei 32,2 U/l (13,7 - 50,7). Ohne Genotyp-Korrektur liegt der Mittelwert bei 48,0 U/l (15,0 - 80,9). Die Unterschiede zwischen den drei Genotypgruppen sind jeweils hochsignifikant (p < 0,0001).

Schlussfolgerung: Die einmalige Bestimmung des Deletions-/Insertions-Polymorphismus des ACE-Gens und die Anwendung neuer genotypkorrigierter Normbereiche erlaubt eine bessere Interpretation der gemessenen ACE-Aktivität im Serum.

Corrected normal values for serum ACE by genotyping the deletion-/insertion-polymorphism of the ACE gene:

Background: In sarcoidosis, serum ACE is widely recognised as a marker of disease activity. Since 1990 a deletion-/insertion polymorphism of the ACE gene is known and a correlation between the genotypes of this polymorphism and serum ACE levels has been observed. Homzygotes for the deletion allele (DD) have the highest levels and homozygotes for the insertion allele (II) the lowest. Heterozygote (DI) persons show intermediate levels. The extent of this influence varies in populations of different ethnic origin. In a large cohort of healthy individuals from North of Germany, genotype-based normal ranges for serum ACE were determined for the population of Germany for the first time.

Methods: In 262 healthy individuals the genotype of the ACE D/I gene polymorphism was determined from genomic DNA by a PCR method. In addition, in serum samples of all these individuals ACE level was measured with a kinetic test.

Results: The genotype DD was found in 29.4 % of the individuals examined, the genotype DI in 49.6 % and the genotype II in 21.0 %, respectively. These results are similar to those found in previous investigations in other populations of Central European origin. The mean serum ACE levels (95 % confidence interval) in individuals with the genotypes DD, DI and II are 59.8 U/l (31.8 - 87.8), 47.7 U/l (18.6 - 76.8) and 32.2 U/l (13.7 - 50.7), respectively. Without taking the genotype into account, the average value is 48.0 U/l (15.0 - 80.9). Differences between all genotype groups are highly significant (p < 0.0001).

Conclusions: In sarcoidosis patients, the determination of this ACE gene polymorphism once in the course of the disease allows a better interpretation of the serum ACE levels measured.

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Dr. med. B. Ruprecht

Medizinische Klinik
Forschungszentrum Borstel

Parkallee 35

23845 Borstel

Email: E-mail: brup@fz-borstel.de

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