| BackgroundRheumatoid arthritis(RA)is a common chronic,highly disabling autoimmune disease.In developed countries,the prevalence rate was 0.5%-1.0%,and in China,0.42%.RA cannot be well controlled,which not only seriously affects the quality of life of patients,but also increases the financial burden of patients and their families.The pathogenesis of RA is complex and there is no specific treatment for RA.Tripterygium Wilfordii Hook.f.(TwHF)is a traditional Chinese medicine in China.It is one of the most effective and widely used traditional Chinese medicine in the treatment of rheumatoid arthritis.With the development of pharmacogenomics,individualized drug use will be realized.Cytochrome CYP3A4 is an important drug metabolizing enzyme.The individual difference of therapeutic effect of Triptolide in treating rheumatoid arthritis may be related to the polymorphism of CYP3A4 gene.Part 1Objective To investigate the correlation between CYP3A4 and rheumatoid arthritis.MethodsBased on CNKI retrieval strategy establishment,Wan Fang,VIP,CBM,Chi CTR,PubMed,Embase,Clinical Trials,Web of Science and the Cochrane Library database retrieval,for the retrieved articles and reviews,find and read the references,and avoid the testers,retrieval time limit for the database from the database to December 2019,the literature for the Chinese and English languages.The inclusion and exclusion criteria were strictly followed,and the acquisition of data was completed independently by 2 researchers.If it meets the requirements of Meta analysis,RevMan 5.3 software will be used for data analysis;if it does not meet the requirements of Meta analysis,descriptive analysis will be conducted.ResultThe two case series studies that were included showed that the detection level of 4-OHC,an endogenous CYP3A4 metabolite,was correlated with the expression level of cytokines during RA treatment.ConclusionSystematic review suggested a correlation between CYP3A4 and the efficacy of rheumatoid arthritis,but lack of high-level evidence-based medicine evidence.Part 2ObjectiveTo investigate the correlation between CYP3A4 gene polymorphism and individual differences in the therapeutic effect of Tripterygium wil fordii on rheumatoid arthri tis.Methods58 RA patients taking tripterygium glycosides tablets by mouth were collected to determine the therapeutic effect and 58 patients with CYP3A4 single nucleotide polymorphism(SNP)were detected by SnaPshot method.Hardy-Weinberg equilibrium verification and correlation test were performed using Pearson Chi-Square test.P<0.05 was considered statistically significant.The relationship between CYP3A4 genotype and the therapeutic effect of tripterygium wilfordii in patients with rheumatoid arthritis was analyzed by binary Logistic regression model.Result58 patients with genotype to Hardy-Weinberg genetic balance(P>0.5),the three genotypes(GG,GA,AA)efficient difference was statistically significant,when comparing two GG type and there was no statistically significant difference in the efficient AA type,and GG type and GA,GA and AA type efficient difference was statistically significant between groups.In the small sample binary Logistic regression model analysis,it was predicted that tripterygium wilford-ii was most effective in RA patients with CYP3A4 rs2740574,followed by GA and GG.ConclusionThe individual difference of therapeutic effect of tripterygium wilfordii in patients with rheumatoid arthritis was related to SNP polymorphism of CYP3A4 gene. |
