The effect of 3435C>T MDR1 gene polymorphism on rheumatoid arthritis treatment with disease-modifying antirheumatic drugs.
OBJECTIVE
Rheumatoid arthritis (RA) is a multifactorial disease, with immunological, genetical as well as environmental factors being implicated in its pathogenesis. Treatment of RA is based mainly on drugs modulating the course of the disease, e.g. methotrexate (MTX) or sulfasalazine (SL). The MDR1 gene product, P-glycoprotein (P-gp), is probably one of the most important and best defined transporters for drug delivery in humans. P-gp transports a wide range of substrates with diverse chemical structures, among them anticancer agents, cardiac drugs, and immunosuppressants. The aim of this study was to examine the effect of the 3435C>T MDR1 gene polymorphism on the efficacy of RA treatment with disease-modifying antirheumatic drugs, i.e. MTX plus methylprednisolone (MP), and SL.


METHODS
The study was carried out on 255 patients with RA treated according to two regimes: (1) MTX (7.5-15.0 mg weekly) plus low doses of MP (n=174), (2) SL (1.5-3 g daily, n=81).


RESULTS
The probability of remission of RA symptoms after MTX plus MP therapy was 4.65-fold higher in carriers of the TT genotype compared to patients with CC genotype (P=0.003, OR 4.65, 95%CI 1.66-13.05), whereas the probability of remission of RA symptoms in patients treated with SL was 2-fold higher in carriers of TT genotype compared to patients with CC genotype, but did not reach statistical significance (P=0.358, OR=2.00 95% CI=0.58-6.87).


CONCLUSIONS
The results from the present study suggest that the 3435C>T MDR1 gene polymorphism may influence the efficacy of RA therapy with disease-modifying antirheumatic drugs.
Drozdzik
Marek
M
Department of Pharmacology, Pomeranian Medical University, ul. Powstancow Wlkp. 72, 70-111, Szczecin, Poland.
Rudas
Tomasz
T
Pawlik
Andrzej
A
Kurzawski
Mateusz
M
Czerny
Bogusław
B
Gornik
Wanda
W
Herczynska
Magdalena
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012460:Sulfasalazine / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018501:Antirheumatic Agents; D012460:Sulfasalazine; D008775:Methylprednisolone; D008727:Methotrexate