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- Title
The G-Allele of the PSMA6−8C>G polymorphism is associated with poor outcome in multiple myeloma independently of circulating proteasome serum levels.
- Authors
Bachmann, Hagen S.; Novotny, Jürgen; Sixt, Stephan; Liebisch, Peter; Frey, Ulrich H.; Dührsen, Ulrich; Siffert, Winfried; Nückel, Holger
- Abstract
Introduction: The proteasome system plays a crucial role in several malignant disorders, especially in multiple myeloma (MM). The G-allele of a single nucleotide polymorphism (SNP) −8C>G in the gene PSMA6, one of seven α-subunit genes of the 20S proteasome, was associated with myocardial infarction. Moreover, PSMA6 mRNA expression in human B-cell lines depended on genotypes. We investigated a potential role of this novel SNP in patients with MM. Methods: PSMA6 genotypes of 116 patients with MM were associated with survival. Circulating proteasome levels (CPL) dependent on −8C>G genotypes of 70 newly diagnosed patients were studied using an anti-20S proteasome enzyme-linked immunoabsorbant assay (ELISA). Results: Genotype distribution (69 CC, 44 CG, 3 GG) was compatible with Hardy–Weinberg equilibrium. Kaplan–Meier curves revealed a significant association of PSMA6−8C>G with 5-yr survival ( P = 0.014). Median survival time was 43 months for the GG genotype and 50 months for the CG genotype. It was not reached within follow-up by the CC genotype (CC 5-yr survival rate 61.2%). Following hazard ratio (HR) for overall survival was calculated: G-allele vs. CC genotype: 2.038, 95% CI 1.14–3.65, P = 0.017. In multivariate analysis the G-allele was an independent prognostic factor (HR 2.1, P = 0.014). CPL were not significantly different between genotypes [mean CPL: CC 284.9 ng/mL vs. 303.3 ng/mL G-allele carriers ( P = 0.709)]. Conclusions: These results suggest the G-allele of the PSMA6−8C>G polymorphism as a possible survival prognosticator.
- Subjects
MYOCARDIAL infarction; ENZYME-linked immunosorbent assay; MULTIPLE myeloma; HARDY-Weinberg formula; GENETIC polymorphisms
- Publication
European Journal of Haematology, 2010, Vol 85, Issue 2, p108
- ISSN
0902-4441
- Publication type
Article
- DOI
10.1111/j.1600-0609.2010.01455.x