Genetic polymorphisms in folate pathway enzymes  as a possible marker for predicting the outcome of  methotrexate therapy in Japanese patients with  rheumatoid arthritis.
BACKGROUND
Low-dose methotrexate (MTX) therapy is widely used in the treatment of rheumatoid arthritis (RA). Though the difference in response to MTX between patients with RA is large, the factors that contribute to this variability remain unclear.


OBJECTIVE
We aimed to identify those factors with a particular emphasis on the pharmacogenetics of MTX.


METHODS
We evaluated the association of possible factors, including genetic polymorphisms of folate metabolic pathway enzymes, with the cumulative value of C-reactive protein, an index of MTX anti-inflammatory efficacy, in 87 Japanese patients with RA.


RESULTS
Polymorphisms of the reduced folate carrier gene (RFC) G80A and of the gamma-glutamylhydrolase gene (GGH) C-401T were more closely associated (beta = 2.1194, P = 0.0017) than other polymorphisms, with the anti-inflammatory response to MTX.


CONCLUSIONS
Patients with RA having RFC 80A and GGH-401T alleles were less responsive to MTX than those with RFC 80A and without GGH-401T alleles. Thus, this data may be useful for guiding treatment of RA patients with MTX.
Hayashi
H
H
Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
Fujimaki
C
C
Daimon
T
T
Tsuboi
S
S
Matsuyama
T
T
Itoh
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D058978:Reduced Folate Carrier Protein; D011623:gamma-Glutamyl Hydrolase / Q000235:genetics
D018501:Antirheumatic Agents; D054316:Biomarkers, Pharmacological; D026901:Membrane Transport Proteins; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D002097:C-Reactive Protein; D011623:gamma-Glutamyl Hydrolase; D008727:Methotrexate