Investigation of the DHODH Genetic Polymorphism (19C ＞ A) Response to Leflunomide Treatment in Rheumatoid Arthritis / 医学研究杂志

ABSTRACT

Objective Purpose leflunomide (LEF) is a disease-modifying antirheumatic drug used for treating rheumatoid arthritis (RA).It is a prodrug that is rapidly converted in vivo to the active metabolite A77 1726.The mechanism of action of A77 1726 primarily involves inhibition of the enzyme DHODH.Related studies have found that DHOD gene has polymorphism.The aim of this study was to investigate whether genetic polymorphisms in DHODH (19C ＞ A) influence leflunomide pharmacokinetics and treatment response.Methods We studied 105 patients diagnosed with RA and treated with LEF (20 mg daily).Follow-up was 6 months.Clinical improvement was valuated according to the American College of Rheumatology 20％ and 50％ response criteria.The peripheral blood genomic DNA was extracted,and amplified by PCR,analyzed by direct sequencing.The gene detection was performed in our hospital 105 patients with DHODH polymorphism(19C ＞ A).Results After 3 months of therapy,the ACR20 criteria was met by 70.0％ in C allele,51.7％ in A allele.Differences were statistically significant(P =0.012).The ACR50 criteria was met by 38.0％ in C allele,28.3％ in A allele.It did not reach statistically significant(P =0.185).After 6 months of therapy,the ACR20 criteria was met by 84.7％ in C allele,61.7％ in A allele.Differences were statistically significant (P =0.006).The ACR50 criteria was met by 60.7％ in C allele,38.3 ％ in A allele.Differences were statistically significant(P =0.039).Conclusion The remission rate of ACR20 and ACR50 in patients with rheumatoid arthritis was increased with the treatment time.The results of the study suggest that DHODH(19C ＞ A) polymorphism may be associated with LEF treatment outcome in RA patients.Treatment response is better in the patients with the C allele than A allele.This trend is more obvious with the extension of time.