24967362
OBJECTIVE	Methotrexate ( MTX ) , the most used drug in rheumatoid arthritis ( RA ) treatment , showing variability in clinical response , is often associated with genetic polymorphisms .
OBJECTIVE	This study aimed to elucidate the role of methylenetetrahydrofolate reductase ( MTHFR ) C677T and aminoimidazole carboxamide adenosine ribonucleotide transformylase ( ATIC ) T675C polymorphisms and clinicopathological variables in clinical response to MTX in Portuguese RA patients .
METHODS	Study included 233 RA patients treated with MTX for at least six months .
METHODS	MTHFR C677T and ATIC T675C polymorphisms were genotyped and clinicopathological variables were collected .
METHODS	Statistical analyses were performed and binary logistic regression method adjusted to possible confounding variables .
RESULTS	Multivariate analyses demonstrated that MTHFR 677TT ( OR = 4.63 ; P = 0.013 ) and ATIC 675T carriers ( OR = 5.16 ; P = 0.013 ) were associated with over 4-fold increased risk for nonresponse .
RESULTS	For clinicopathological variables , noncurrent smokers ( OR = 7.98 ; P = 0.001 ) , patients positive to anti-cyclic citrullinated peptide ( OR = 3.53 ; P = 0.004 ) and antinuclear antibodies ( OR = 2.28 ; P = 0.045 ) , with higher health assessment questionnaire score ( OR = 2.42 ; P = 0.007 ) , and nonsteroidal anti-inflammatory drug users ( OR = 2.77 ; P = 0.018 ) were also associated with nonresponse .
RESULTS	Contrarily , subcutaneous administration route ( OR = 0.11 ; P < 0.001 ) was associated with response .
CONCLUSIONS	Our study suggests that MTHFR C677T and ATIC T675C genotyping combined with clinicopathological data may help to identify patients whom will not benefit from MTX treatment and , therefore , assist clinicians in personalizing RA treatment .

