We evaluated the association between germline genetic variants located within the 3 '-untranlsated region (polymorphic 3 ' UTR, ie, p3UTR) of candidate genes involved in multiple myeloma (MM). We performed a case-control study within the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 3056 MM patients and 1960 controls recruited from eight countries. We selected p3UTR of six genes known to act in different pathways relevant in MM pathogenesis, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434), SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496). We found that IL10-rs3024496 was associated with increased risk of developing MM and with a worse overall survival of MM patients. The variant allele was assayed in a vector expressing eGFP chimerized with the IL10 3 '-UTR and it was found functionally active following transfection in human myeloma cells. In this experiment, the A-allele caused a lower expression of the reporter gene and this was also in agreement with the in vivo expression of mRNA measured in whole blood as reported in the GTEx portal. Overall, these data are suggestive of an effect of the IL10-rs3024496 SNP on the regulation of IL10 mRNA expression and it could have clinical implications for better characterization of MM patients in terms of prognosis.

Melaiu, O., Macauda, A., Sainz, J., Calvetti, D., Facioni, M.s., Maccari, G., et al. (2021). Common gene variants within 3′-untranslated regions as modulators of multiple myeloma risk and survival. INTERNATIONAL JOURNAL OF CANCER, 148(8), 1887-1894 [10.1002/ijc.33377].

Common gene variants within 3′-untranslated regions as modulators of multiple myeloma risk and survival

Melaiu O.;
2021

Abstract

We evaluated the association between germline genetic variants located within the 3 '-untranlsated region (polymorphic 3 ' UTR, ie, p3UTR) of candidate genes involved in multiple myeloma (MM). We performed a case-control study within the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 3056 MM patients and 1960 controls recruited from eight countries. We selected p3UTR of six genes known to act in different pathways relevant in MM pathogenesis, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434), SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496). We found that IL10-rs3024496 was associated with increased risk of developing MM and with a worse overall survival of MM patients. The variant allele was assayed in a vector expressing eGFP chimerized with the IL10 3 '-UTR and it was found functionally active following transfection in human myeloma cells. In this experiment, the A-allele caused a lower expression of the reporter gene and this was also in agreement with the in vivo expression of mRNA measured in whole blood as reported in the GTEx portal. Overall, these data are suggestive of an effect of the IL10-rs3024496 SNP on the regulation of IL10 mRNA expression and it could have clinical implications for better characterization of MM patients in terms of prognosis.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/18
English
3′-untranslated region
multiple myeloma
overall survival
risk
single nucleotide polymorphisms
susceptibility
3' Untranslated Regions
Adult
Aged
Case-Control Studies
Female
Gene Expression Regulation, Neoplastic
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
Male
Middle Aged
Multiple Myeloma
Polymorphism, Single Nucleotide
RNA, Messenger
Risk Factors
Survival Analysis
Germ-Line Mutation
Melaiu, O., Macauda, A., Sainz, J., Calvetti, D., Facioni, M.s., Maccari, G., et al. (2021). Common gene variants within 3′-untranslated regions as modulators of multiple myeloma risk and survival. INTERNATIONAL JOURNAL OF CANCER, 148(8), 1887-1894 [10.1002/ijc.33377].
Melaiu, O; Macauda, A; Sainz, J; Calvetti, D; Facioni, Ms; Maccari, G; ter Horst, R; Netea, Mg; Li, Y; Grzasko, N; Moreno, V; Jurczyszyn, A; Jerez, A; Watek, M; Varkonyi, J; Garcia-Sanz, R; Kruszewski, M; Dudzinski, M; Kadar, K; Jacobsen, Seh; Mazur, G; Andersen, V; Rybicka, M; Zawirska, D; Razny, M; Zaucha, Jm; Ostrovsky, O; Iskierka-Jazdzewska, E; Reis, Rm; Stepien, A; Beider, K; Nagler, A; Druzd-Sitek, A; Marques, H; Martinez-Lopez, J; Lesueur, F; Avet-Loiseau, H; Vangsted, Aj; Krawczyk-Kulis, M; Butrym, A; Jamroziak, K; Dumontet, C; Vogel, U; Rymko, M; Pelosini, M; Subocz, E; Szombath, G; Sarasquete, Me; Silvestri, R; Morani, F; Landi, S; Campa, D; Canzian, F; Gemignani, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/305987
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