The MDR1 3435 polymorphism in patients with rheumatoid arthritis.
OBJECTIVE
Rheumatoid arthritis (RA) is a multifactorial disease, the pathogenesis of which involves immunological, genetic and environmental factors. P-glycoprotein (P-gp) encoded by the MDR1 gene, is an important transporter for many drugs, xenobiotics and cytokines and may be associated with many immunological processes and apoptosis. The activity of P-gp is genetically determined. Naturally occurring MDR1 polymorphisms have been described and correlated with potential clinical effects. Several mutations in the MDR1 gene have been recognized, but only some of them are associated with P-gp expression. The C3435T polymorphism was found to correlate with the activity of P-glycoprotein. The aim of the study was to evaluate the C3435T MDR1 polymorphism in patients with rheumatoid arthritis and to investigate a possible correlation with disease susceptibility, activity and severity.


METHODS
The study was carried out in 92 patients with rheumatoid arthritis and 97 healthy subjects as a control group. The C3435T polymorphism was determined using the PCR-RFLP method.


RESULTS
The distribution of C3435TT MDR1 genotypes in RA patients did not differ significantly from that in a control group and was as follows: 3435CC in 25 (26.9%) subjects, 3435CT in 50 (53.8%) and 3435TT in 17 (18.3%). The probability of remission of RA symptoms after therapy with methotrexate and glucocorticosteroids however, was 2.89-fold greater in patients with the 3435TT genotype compared to patients with the genotypes 3435CC and 3435CT. The risk of having an active form of rheumatoid arthritis resistant to therapy with disease-modifying antirheumatic drugs in patients with 3435CC and 3435CT genotypes was 2.89 times greater than in homozygous 3435TT subjects.


CONCLUSIONS
We suggest that the C3435T MDR1 polymorphism is not an important genetic risk factor for RA susceptibility, but that this polymorphism may have an influence on the activity of the disease and its response to therapy with disease-modifying antirheumatic drugs.
Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, ul Powstanców Wielkopolskich 72, Poland. pawand@poczta.onet.pl
A
A
Pawlik
J
J
Wrzesniewska
I
I
Fiedorowicz-Fabrycy
B
B
Gawronska-Szklarz
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000032:analysis; D017931:DNA Primers; D005260:Female; D019450:Genes, MDR / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D017931:DNA Primers; D004247:DNA