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


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.
Chiusolo
Patrizia
P
Hematology Department, Università Cattolica del Sacro Cuore, L.go Gemelli 8, 00168, Rome, Italy. p.chiusolo@rm.unicatt.it
Farina
Giuliana
G
Putzulu
Rossana
R
Reddiconto
Giovanni
G
Fiorini
Alessia
A
De Stefano
Valerio
V
Rossi
Elena
E
Palladino
Mariangela
M
Leone
Giuseppe
G
Sica
Simona
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D014644:Genetic Variation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007136:Immunoglobulins / Q000097:blood; D008297:Male; D008745:Methylation; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007136:Immunoglobulins; D042965:Methylenetetrahydrofolate Reductase (NADPH2)