Methylenetetrahydrofolate reductase genotypes do not play a role in acute lymphoblastic leukemia pathogenesis in the Italian population.
OBJECTIVE
Methylenetetrahydrofolate reductase (MTHFR) is one of the enzymes involved in folate metabolism and DNA methylation and synthesis. Some genotypes of this highly polymorphic enzyme are associated with decreased activity. Previous studies have suggested that individuals with the MTHFR 677TT, 1298AC and 1298CC have a lower risk of adult acute lymphoblastic leukemia (ALL).


METHODS
In order to test this association we studied the presence of the C677T and A1298C mutant alleles in 174 patients with acute lymphoblastic leukemia and in 110 controls from central Italy.


RESULTS
We did not find any association between the different polymorphisms and susceptibility to ALL. In multivariate analysis different genotypes did not show any correlation with the risk of ALL. The adjusted odds ratios and 95% confidence intervals for MTHFR C677T were 0.69 (0.4-1.19) for 677CT versus 677CC wild type, and 0.99 (0.50-1.97) for 677TT versus 677CC. The corresponding values for MTHFR A1298C were 0.93 (0.56-1.53) for 1298AC versus 1298AA wild type and 1.14 (0.36-3.61) for 1298CC versus 1298AA.


CONCLUSIONS
These results do not support the suggestion that populations carrying different genotypes of the two MTHFR polymorphisms, C677T and A1298C, have a different susceptibility to ALL, at least in the Mediterranean area.
Istituto di Ematologia, Policlinico Gemelli, Largo A. Gemelli 8, 00168 Rome, Italy. p.chiusolo@rm.unicatt.it
Patrizia
P
Chiusolo
Giovanni
G
Reddiconto
Giuseppe
G
Cimino
Simona
S
Sica
Alessia
A
Fiorini
Giuliana
G
Farina
Antonella
A
Vitale
Federica
F
Sorà
Luca
L
Laurenti
Francesco
F
Bartolozzi
Paola
P
Fazi
Franco
F
Mandelli
Giuseppe
G
Leone
D000483:Alleles; D019943:Amino Acid Substitution; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000453:epidemiology / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000502:physiology; D020125:Mutation, Missense; D017354:Point Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D015995:Prevalence; D012306:Risk
D042965:Methylenetetrahydrofolate Reductase (NADPH2)