Polymorphismen der Glutathion-S-Transferase A1 in Zusammenhang mit malignen hämatologischen Erkrankungen

by Anja Siede
Doctoral thesis
Date of Examination:2010-10-16
Date of issue:2010-08-20
Advisor:PD Dr. Thomas Schulz
Referee:Prof. Dr. Ernst Hallier
Referee:Prof. Dr. Detlef Haase
Referee:Prof. Dr. Patricia Virsik-Köpp
Persistent Address: http://dx.doi.org/10.53846/goediss-840

 

 

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Abstract

English

Since a long time xenobiotic metabolizing enzymes are an object of investigation. There are a series of polymorphisms described which are associated with a high susceptibility to develop several malignant tumors. Additional some of these polymorphisms seem to be associated with an increased risk for secondary malignancies like leukemias or myelodysplastic syndrom. The family of glutathione S-transferases play a central role in detoxification of xenobiotics - therefore the investigation of their polymorphisms is exceptionally relavant. The hGSTA1*B polymorphism in the proximal promotor of the GSTA1 correlates with a differential activity and therefore it is responsible for a decreased expression of the enzyme. We investigated by polymerase chain reaktion and PCR-restriction fragment length polymorphism wether the hGSTA1*B variant cumulates in patients with AML or MDS as primary or secondary disease. In the group of patients with AML (primary AML) had 9,5% the hGSTA1*B genotype, whereas in the group of patients with MDS (primary MDS) hold 11,7% these genevariant. Both data differ not significant related to the normal controls (12,1%). The t-AML group had 5% hGSTA1*B genetypes. No individual with t-MSD had the homozygous hGSTA1*B variant. Against initial assumption therefore were no significant increase of the hGSTA1*B genotype in t-AML- or t-MDS-patients. Our investigations could not establish a relationship between the hGSTA1*B polymorphism and primary or secondary AML/ MDS.
Keywords: Polymorphismus; GSTA1; maligne hämatologische Erkrankungen

Other Languages

Seit längerem sind Fremdstoff-metabolisierende Enzyme (FME) Untersuchungsgegenstand verschiedener Forschungsgruppen. Es wurde eine Reihe von Polymorphismen der FME beschrieben, die mit einer erhöhten Suszeptibilität bezüglich der Entstehung verschiedener Malignome assoziiert werden konnten. Zusätzlich scheinen einige dieser Polymorphismen mit einem erhöhten Risiko in Bezug auf die Entwicklung sekundärer maligner Erkrankungen wie Leukämien oder Myelodysplastisches Syndrom verbunden zu sein. Da die Familie der Glutathion-S-Transferasen innerhalb des Phase-II-Stoffwechsels eine zentrale Rolle in der Entgiftung spielen, waren und sind auch ihre Polymorphismen äußerst forschungsrelevant.
Schlagwörter: Polymorphismus; GSTA1; maligne hämatologische Erkrankungen
 
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