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Updated: Jul 21, 2026
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Analysis of MTHFR polymorphisms and P16 methylation and their correlation with clinical-biological features of
Patrizia Chiusolo1, Giuliana Farina, Rossana Putzulu
1Hematology Department, Università Cattolica del Sacro Cuore, L.go Gemelli 8, 00168, Rome, Italy. p.chiusolo@rm.unicatt.it
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.
Insights
Methylenetetrahydrofolate reductase (MTHFR) gene variants do not significantly alter multiple myeloma (MM) risk. However, MTHFR 677CC genotype is linked to increased p16 hypermethylation in MM patients.
Area of Science:
- Genetics
- Oncology
- Nutritional Biochemistry
Background:
- Low folate intake and MTHFR gene polymorphisms are implicated in cancer development.
- Previous studies on MTHFR variants and multiple myeloma (MM) risk have yielded conflicting results.
Purpose of the Study:
- To investigate the association between MTHFR gene polymorphisms (C677T and A1298C) and the risk of developing multiple myeloma (MM).
- To examine the relationship between MTHFR genotypes and p16 methylation status in MM patients.
Main Methods:
- A matched case-control study was conducted.
- Genotyping for MTHFR C677T and A1298C polymorphisms was performed.
- p16 methylation status was analyzed in MM patients.
Main Results:
- No significant association was found between MTHFR C677T or A1298C variants and MM susceptibility.
- A high prevalence of p16 methylation (40%) was observed in MM patients.
- The MTHFR 677CC genotype was associated with a higher prevalence of p16 hypermethylation.
Conclusions:
- MTHFR gene variants do not appear to play a significant role in MM risk or protection.
- Dietary folate intake may modify the effect of MTHFR polymorphisms on MM.
- p16 hypermethylation is a common genetic alteration in MM and may contribute to its pathogenesis.
