Methylenetetrahydrofolate reductase polymorphisms and methotrexate: no association with response to therapy nor with drug-related adverse events in an Italian population of rheumatic patients.
OBJECTIVE
MTHFR is an enzyme involved in the folate pathway. It has been suggested that common polymorphisms in its gene (C677T and A1298C) could be related to different methotrexate (MTX) response and toxicity in rheumatoid arthritis (RA) patients. Agreement has not been found yet and there is no data on rheumatic Italian patients. The aim of this study is to determine if a genetic screening can help in planning the treatment in these patients.


METHODS
We enrolled 84 Northern Italian patients affected by RA (n=79), psoriatic arthritis (n=4) and ankylosing spondylitis (n=1), who received MTX. Subjects who achieved at least ACR20 response in 6 months and maintained it during the following 6 months were defined as "responders"; those who did not obtain a disease control after 6 months of MTX were classified as "non responders". Patients who experienced MTX adverse events were defined "with toxicity", those who did not, as "without toxicity". Genotypes were determined by polymerase chain reaction.


RESULTS
Genotype frequency was consistent with that reported in a healthy population from Italy. We did not find any statistically significant difference in genotype/allele distribution between the groups. In patients receiving folic acid supplementation MTX toxicity was recorded only in 18 cases (24%), while all the 8 patients not receiving it experienced MTX adverse events (p=0.00).


CONCLUSIONS
In our study we did not find any association between MTHFR genotype/allele and MTX response or toxicity. At the moment there is not sufficient evidence for MTHFR screening in patients who are candidate for MTX.
Taraborelli
M
M
U.O. Reumatologia e Immunologia Clinica, Spedali Civili e Università degli Studi, 25123 Brescia, Italy.
Andreoli
L
L
Archetti
S
S
Ferrari
M
M
Cattaneo
R
R
Tincani
A
A
D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000188:drug therapy* / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate