- Tytuł:
- Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients
- Autorzy:
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Giles, Graham G.
Ziv, Elad
Clay-Gilmou, Alyssa I.
Dudziński, Marek
Ebbesen, Lene Hyldahl
Markiewicz, Mirosław
Mazur, Grzegorz
Martinez-Lopez, Joaquin
Grzasko, Norbert
Jurczyszyn, Artur
Vangsted, Annette Juul
Norman, Aaron D.
Druzd-Sitek, Agnieszka
Brown, Elizabeth E.
Iskierka-Jazdzewska, Elzbieta
Andersen, Niels Frost
Rymko, Marcin
Milne, Roger L.
Garcia-Sanz, Ramon
Kruszewski, Marcin
Jamroziak, Krzysztof
Zawirska, Daria
Pelosini, Matteo
Barington, Torben
Marques, Herlander
Camp, Nicola J.
Vachon, Celine M.
Waller, Rosalie G.
Piredda, Chiara
Campa, Daniele
Prejzner, Witold
Raźny, Małgorzata
Tomczak, Waldemar
Suska, Anna
Dutka, Magdalena
Butrym, Aleksandra
Macauda, Angelica
Berndt, Sonja
Belachew, Alem A.
Gemignani, Federica
Hildebrandt, Michelle A.T.
Buda, Gabriele
Dumontet, Charles
Subocz, Edyta
Varkonyi, Judit
Reis, Rui Manuel
Abildgaard, Niels
Canzian, Federico
Sainz, Juan
Wątek, Marzena
Slager, Susan L.
Spinelli, John
Haastrup, Eva Kannik
Hofmann, Jonathan N. - Opis:
- Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype-tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < $10^{-7}$ either in EBV-transformed B-lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression-free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4-rs1992292, TBRG4- rs2287535 and ENTPD1-rs2153913) showed associations with OS at P < .05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta-analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4-rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04-1.26, P = .007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients.
- Dostawca treści:
- Repozytorium Uniwersytetu Jagiellońskiego
Artykuł