The effect of exon (19C>A) dihydroorotate dehydrogenase gene polymorphism on rheumatoid arthritis treatment with leflunomide

Pharmacogenomics

Volumn 10, Issue 2, 2009, Pages 303-309

  Pawlik, Andrzej ^a   Herczynska, Magdalena ^b   Kurzawski, Mateusz ^a   Safranow, Krzysztof ^a   Dziedziejko, Violetta ^a   Drozdzik, Marek ^a  

^a POMERANIAN MEDICAL UNIVERSITY   (Poland)

^b Department of Laboratory Medicine   (Poland)

Author keywords

Dihydroorotate dehydrogenase; Leflunomide; Polymorphism; Rheumathoid arthritis

Indexed keywords

DIHYDROOROTATE DEHYDROGENASE; DISEASE MODIFYING ANTIRHEUMATIC DRUG; LEFLUNOMIDE; ANTIRHEUMATIC AGENT; ISOXAZOLE DERIVATIVE; OXIDOREDUCTASE; PRIMER DNA;

ADULT; AMINO ACID SUBSTITUTION; ARTICLE; CONTROLLED STUDY; ERYTHROCYTE COUNT; EXON; FEMALE; GENE FREQUENCY; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENOTYPE; HEMOGLOBIN BLOOD LEVEL; HUMAN; MAJOR CLINICAL STUDY; MALE; OUTCOME ASSESSMENT; REMISSION; RHEUMATOID ARTHRITIS; SIDE EFFECT; THERAPY EFFECT; THROMBOCYTE COUNT; TREATMENT OUTCOME; TREATMENT RESPONSE; ENZYMOLOGY; GENETICS; HETEROZYGOTE; MIDDLE AGED; NUCLEOTIDE SEQUENCE; POLYMERASE CHAIN REACTION; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; SINGLE NUCLEOTIDE POLYMORPHISM;

ADULT; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; CARRIER STATE; CONSERVED SEQUENCE; DNA PRIMERS; EXONS; FEMALE; GENOTYPE; HUMANS; ISOXAZOLES; MALE; MIDDLE AGED; OXIDOREDUCTASES ACTING ON CH-CH GROUP DONORS; POLYMERASE CHAIN REACTION; POLYMORPHISM, GENETIC; POLYMORPHISM, RESTRICTION FRAGMENT LENGTH; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 65549117845     PISSN: 14622416     EISSN: 17448042     Source Type: Journal    
DOI: 10.2217/14622416.10.2.303     Document Type: Article

References (25)

1. Brazelton TR, Morris RE: Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Curr. Opin. Immunol. 8, 710-720 (1996).
2. Davis JP, Cain GA, Pitts WJ, Magolda RL, Copeland RA: The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase. Biochemistry 35, 1270-1273 (1996).
3. Herrmann ML, Schleyerbach R, Kirschbaum BJ: Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology 47, 273-289 (2000).
4. Fairbanks LD, Jacomelli G, Micheli V, Slade T, Simmonds HA: Severe pyridine nucleotide depletion in fibroblasts from Lesch-Nyhan patients. Biochem. J. 366, 265-272 (2002).
5. Chen JJ, Jones ME: The cellular location of dihydroorotate dehydrogenase: relation to de novo biosynthesis of pyrimidines. Arch. Biochem. Biophys. 176, 82-90 (1976).
6. Rawls J, Knecht W, Diekert K, Lill R, Löffler M: Requirements for the mitochondrial import and localization of dihydroorotate dehydrogenase. Eur. J. Biochem. 267, 2079-2087 (2000).
7. Neupert W: Protein import into mitochondria. Annu. Rev. Biochem. 66, 863-917 (1997).
8. Felson DT, Anderson JJ, Boers M: The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials. Arthritis Rheum. 36, 729-740 (1993).
9. Wolfe F, O'Dell JR, Kavanaugh A, Wilske K, Pincus T: Evaluating severity and status in rheumatoid arthritis. J. Rheumatol. 28, 1453-1462 (2001).
10. Pincus T, Summey JA, Soraci SA Jr, Wallston KA, Hummon NP: Assessment of patient satisfaction in activities of daily living using a modified Stanford Health Assessment Questionnaire. Arthritis Rheum. 26, 1346-1353 (1983).
11. Felson DT, Anderson JJ, Boers M: American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 38, 727-735 (1995).
12. Strand V, Cohen S, Schiff M et al.: Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Arch. Intern. Med. 159, 2542-2550 (1999).
13. Smolen JS, Kalden JR, Scott DL et al.: Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group. Lancet 353, 259-266 (1999).
14. Mladenovic V, Domljan Z, Rozman B et al.: Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Results of a randomized, placebo-controlled, Phase II study. Arthritis Rheum. 38, 1595-1603 (1995).
15. Xu X, Williams JW, Bremer EG, Finnegan A, Chong AS: Inhibition of protein tyfosine phosphorylation in T cells by a novel immunosuppressive agent, leflunomide. J. Biol. Chem. 270, 12398-12403 (1995).
16. Litinsky I, Paran D, Levartovsky D et al.: The effects of leflunomide on clinical parameters and serum levels of IL-6, IL-10, MMP-1 and MMP-3 in patients with resistant rheumatoid arthritis. Cytokine 33, 106-110 (2006).
17. Angermüller S, Löffler M: Localization of dihydroorotate oxidase in myocardium and kidney cortex of the rat. An electron microscopic study using the cerium technique. Histochem. Cell Biol. 103, 287-292 (1995).
18. Greene S, Watanabe K, Braatz-Trulson J, Lou L: Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide. Biochem. Pharmacol. 50, 861-867 (1995).
19. Davis JP, Cain GA, Pitts WJ, Magolda RL, Copeland RA: The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase. Biochemistry 35, 1270-1273 (1996).
20. Cherwinski HM, Cohn RG, Cheung P et al.: The immunosuppressant leflunomide inhibits lymphocyte proliferation by inhibiting pyrimidine biosynthesis. J. Pharmacol. Exp. Ther. 275, 1043-1049 (1995).
21. Löffler M, Klein A, Hayek-Ouassini M, Knecht W, Konrad L: Dihydroorotate dehydrogenase mRNA and protein expression analysis in normal and drug-resistant cells. Nucleosides Nucleotides Nucleic Acids 23, 1281-1285 (2004).
22. Lill R, Nargang FE, Neupert W: Biogenesis of mitochondrial proteins. Curr. Opin. Cell Biol. 8, 505-512 (1996).
23. Hurt E, van Loon A: How proteins find mitochondria and intramitochondrial compartments. Trends Biochem. Sci. 11, 204-207 (1986).
24. von Heijne G: Targeting signals for protein import into mitochondria and other subcellular organelles. Adv. Mol. Cell Biol. 17, 1-12 (1997).
25. Hartl E, van Loon A: Protein sorting to mitochondria: evolutionary conservations of folding and assembly. Science 247, 930-938 (1990).