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Oncogene. 2005 Mar 17;24(12):2042-9.

G125A single-nucleotide polymorphism in the human BAX promoter affects gene expression.

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1
Department of Pathology, Royal University Hospital, College of Medicine, University of Saskatchewan, Saskatoon, Canada S7N 0W8.

Abstract

Earlier we had reported a guanine to adenosine substitution at position 125 (G125A) in the BAX promoter, and its association with higher stage of the disease and failure to achieve complete response to treatment in chronic lymphocytic leukemia (CLL) patients. The aim of this study was to test the hypothesis that G125A leads to a reduction in the transcription of the BAX gene and that this is a direct cause of altered BAX mRNA and protein expression. In lymphocytes of CLL patients, BAX mRNA expression was determined by RNase protection assay and Bax protein was detected by immunoblotting. The presence of G125A in the BAX promoter was associated with lower BAX mRNA (P=0.004) and protein (P=0.024) levels. In transient expression assays using wild-type and mutant BAX promoter sequences linked to Luciferase as a reporter, the G125A polymorphism reduced expression of the BAX promoter by 2.6-fold. These studies suggest a mechanism for the biological effect of the G125A.

PMID:
15688029
DOI:
10.1038/sj.onc.1208377
[Indexed for MEDLINE]
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