The Impact of the NOD2/CARD15 Variant (3020insC) and PSMA6 Polymorphism (-8C>G) on the Development and Outcome of Multiple Myeloma
| Autor: | Magdalena Wojcierowska-Litwin, Sylwia Chocholska, Wojciech Styk, Sylwia Popek-Marciniec, Agata Filip, Aneta Szudy-Szczyrek, Iwona Korszeń-Pilecka, Szymon Zmorzyński, Marek Hus |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Article Subject PSMA6 Gastroenterology General Biochemistry Genetics and Molecular Biology Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Genotyping Multiple myeloma General Immunology and Microbiology Bortezomib business.industry General Medicine medicine.disease digestive system diseases 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Proteasome inhibitor Medicine Bone marrow business Progressive disease medicine.drug |
| Zdroj: | BioMed Research International, Vol 2020 (2020) |
| ISSN: | 2314-6141 2314-6133 |
| Popis: | Introduction. Multiple myeloma (MM) is a hematological malignancy characterized by genetic variety. The 3020insC variant of the NOD2/CARD15 gene results in the upregulation of proinflammatory cytokines. Chronic inflammation and abnormal function of the proteasome system may lead to MM development. The polymorphism (-8C>G) in the PSMA6 gene affects proteasome activity. The aim of our study was to analyze the possible relationship of NOD/CARD15 and PSMA6 genes with the risk of development and outcome of MM, as well as the sensitivity to bortezomib (proteasome inhibitor) in cell cultures derived from MM patients. Objects and Methods. Genomic DNA from 100 newly diagnosed MM patients and 100 healthy blood donors was analyzed by methods such as PCR-RFLP (for PSMA6 genotyping) and automated DNA sequencing (for NOD2/CARD15 genotyping). In a subgroup of 50 MM patients, nucleated bone marrow cells were treated with bortezomib in vitro. Results. Patients with PSMA6 CG+GG genotypes had higher chances for progressive disease (OR=5.0, 95% CI 1.07-23.16, p=0.05), shorter overall survival taking into account the type of treatment (p=0.039), and increased risk of death due to MM at the level of tendency (OR=4.74, 95% CI 1.02-21.97, p=0.06). The presence of NOD2/CARD15 3020insC decreased the risk of renal dysfunction in MM (OR=0.23, 95% CI 0.07-0.74, p=0.009). The analyzed changes in NOD2/CARD15 and PSMA6 genes did not impact the MM risk. In an in vitro study, bortezomib increased the number of apoptotic cells at 8 nM and 12 nM between wild-type and 3030insC variants of NOD2/CARD15 (p=0.018 and p=0.03, respectively). Conclusion. The presented results suggest a possible impact of PSMA6 CG+GG genotypes on the MM outcome and the association of the NOD2/CARD15 variant with bortezomib in vitro sensitivity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text