Mixed cryoglobulinemia (MC), is a HCV-related, clinically benign, lymphoproliferative disorder (LPD) that may evolve into a non Hodgkin's lymphoma (NHL). Significant associations were found between two single nucleotide polymorphisms near NOTCH4 (rs2071286) and the HLA class II (rs9461776) genes and HCV-related MC syndrome (MCS). We analyzed NOTCH4 rs2071286 and HLA-II rs9461776 in 3 HCV-related LPD groups (asymptomatic MC, MCS, NHL) with HCV infection without lymphoproliferative disorders. We found a positive relationship between NOTCH4 rs207186 T minor allele frequency (MAF) and patients with HCV-related LPDs at risk of NHL (Chi-square test for trend = 14.84p= 0.0001), in accordance with an over-dominant model in the NHL group (CT vs CC + TT, OR=1.88, 95% CI 1.24-2.83,p= 0.0026). Regarding HLA II rs9461776, G MAF increased in patients with HCV-related LPDs at risk of NHL (Chi-square test for trend = 8.40p= 0.0038), in accordance with a recessive genotypic model in the NHL group (G/G vs A/A + A/G, OR = 11.07, 95% CI 2.37-51.64,p= 0.0022). Both NOTCH4 rs2071286 and HLA-II rs9461776 were present on chromosome 6 and showed D' and r values of linkage disequilibrium (LD) of about 0.5 values, thereby suggesting there is no extensive LD in the HCV+ population. This data shows that the previously demonstrated association between NOTCH4 rs2071286 and HLA-II rs9461776 polymorphisms and HCV-related MCS could be extended to overall patients with HCV-related LPDs. The significant relationship between rs2071286 and rs9461776 MAF and the increased risk for NHL, suggests their use as non-invasive markers to categorize patients at risk of lymphoma.

Notch4 and mhc class II polymorphisms are associated with hcv-related benign and malignant lymphoproliferative diseases / Gragnani, Laura; Fognani, Elisa; De Re, Valli; Libra, Massimo; Garozzo, Adriana; Caini, Patrizio; Cerretelli, Guia; Giovannelli, Andrea; Lorini, Serena; Monti, Monica; Bagnoli, Silvia; Piaceri, Irene; Zignego, Anna Linda. - In: ONCOTARGET. - ISSN 1949-2553. - ELETTRONICO. - 8:(2017), pp. 71528-71535. [10.18632/oncotarget.17655]

Notch4 and mhc class II polymorphisms are associated with hcv-related benign and malignant lymphoproliferative diseases

Gragnani, Laura;Fognani, Elisa;Caini, Patrizio;CERRETELLI, GUIA;Giovannelli, Andrea;LORINI, SERENA;Monti, Monica;Bagnoli, Silvia;Piaceri, Irene;Zignego, Anna Linda
2017

Abstract

Mixed cryoglobulinemia (MC), is a HCV-related, clinically benign, lymphoproliferative disorder (LPD) that may evolve into a non Hodgkin's lymphoma (NHL). Significant associations were found between two single nucleotide polymorphisms near NOTCH4 (rs2071286) and the HLA class II (rs9461776) genes and HCV-related MC syndrome (MCS). We analyzed NOTCH4 rs2071286 and HLA-II rs9461776 in 3 HCV-related LPD groups (asymptomatic MC, MCS, NHL) with HCV infection without lymphoproliferative disorders. We found a positive relationship between NOTCH4 rs207186 T minor allele frequency (MAF) and patients with HCV-related LPDs at risk of NHL (Chi-square test for trend = 14.84p= 0.0001), in accordance with an over-dominant model in the NHL group (CT vs CC + TT, OR=1.88, 95% CI 1.24-2.83,p= 0.0026). Regarding HLA II rs9461776, G MAF increased in patients with HCV-related LPDs at risk of NHL (Chi-square test for trend = 8.40p= 0.0038), in accordance with a recessive genotypic model in the NHL group (G/G vs A/A + A/G, OR = 11.07, 95% CI 2.37-51.64,p= 0.0022). Both NOTCH4 rs2071286 and HLA-II rs9461776 were present on chromosome 6 and showed D' and r values of linkage disequilibrium (LD) of about 0.5 values, thereby suggesting there is no extensive LD in the HCV+ population. This data shows that the previously demonstrated association between NOTCH4 rs2071286 and HLA-II rs9461776 polymorphisms and HCV-related MCS could be extended to overall patients with HCV-related LPDs. The significant relationship between rs2071286 and rs9461776 MAF and the increased risk for NHL, suggests their use as non-invasive markers to categorize patients at risk of lymphoma.
2017
8
71528
71535
Gragnani, Laura; Fognani, Elisa; De Re, Valli; Libra, Massimo; Garozzo, Adriana; Caini, Patrizio; Cerretelli, Guia; Giovannelli, Andrea; Lorini, Seren...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1117417
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