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Analysis of MTHFR polymorphisms and P16 methylation and their correlation with clinical–biological features of multiple myeloma

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Abstract

Background

Low folate intake and changes in folate metabolism due to polymorphisms in the methylentetrahydrofolate reductase (MTHFR) gene have been associated with myelomagenesis. However, controversial data have been published regarding a protective role of variant alleles of MTHFR on MM.

Patients and methods

To investigate the influence of two common polymorphisms of MTHFR C677T and A1298C on the risk of multiple myeloma (MM), we performed a matched case-control study. The methylation status pattern of p16 was also addressed.

Results

The frequency each of 677 CC, 677CT, and 677TT was 31, 44, and 25%, respectively, whereas, the frequency each of 1298 AA, AC, CC was 48, 44, and 8% in MM patients. In the control group, the frequency each of 677CC, 677CT, and 677TT was 36, 45, and 19%, respectively, while the frequency each of 1298 AA, AC, CC was 37, 50, and 13%, respectively. No significant association between susceptibility to MM, 677, and 1298 MTHFR variants was detected. As regards p16 methylation, we confirmed a high prevalence of p16 methylation (40%) in patients affected by MM and demonstrated that MTHFR 677CC is associated with a higher prevalence of p16 hypermethylation.

Conclusions

Our data demonstrated that variant alleles did not play a key role neither in protection nor in increased risk for MM, suggesting that the effect of MTHFR on folate metabolism might be modified by diet intake. Moreover, our findings demonstrated that p16 hypermethylation might be a frequent genetic aberration in MM and may contribute with other molecular aberrations in the pathogenesis of this malignant disorder.

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Acknowledgements

We thank Dr. Francesco Bartolozzi for the statistical analysis. This work was supported in part by Associazione Italiana per la Ricerca sul Cancro (AIRC).

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Authors and Affiliations

  1. Hematology Department, Università Cattolica del Sacro Cuore, L.go Gemelli 8, 00168, Rome, Italy

    Patrizia Chiusolo, Giuliana Farina, Rossana Putzulu, Giovanni Reddiconto, Alessia Fiorini, Valerio De Stefano, Elena Rossi, Mariangela Palladino, Giuseppe Leone & Simona Sica

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  1. Patrizia Chiusolo
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  2. Giuliana Farina
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  3. Rossana Putzulu
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  4. Giovanni Reddiconto
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  5. Alessia Fiorini
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  6. Valerio De Stefano
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  7. Elena Rossi
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  8. Mariangela Palladino
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  9. Giuseppe Leone
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  10. Simona Sica
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Correspondence to Patrizia Chiusolo.

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Chiusolo, P., Farina, G., Putzulu, R. et al. Analysis of MTHFR polymorphisms and P16 methylation and their correlation with clinical–biological features of multiple myeloma. Ann Hematol 85, 474–477 (2006). https://doi.org/10.1007/s00277-006-0097-1

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  • DOI: https://doi.org/10.1007/s00277-006-0097-1

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