Developing The Chinese Pharmacogenomics Database And Observing The Effects Of CYP3A And ABCB1Polymorphisms On Cyclosporine A Pharmacokinetics In Early Post-Renal Transplant Recipients

The rapid development of bioinformatics profits from the Human Genome Project. The bioinformatics is a kind of combination of molecular biology with information technology, especially on Internet, taking advantage of mathematics, informatics, statistics and computer to solve the biological problems. It is used for dealing with a huge of biological data by collection, processing, computing, simulation and so forth.The pharmacogenomics as a branch discipline of genomics has been greatly affected by bioinformatics so that it is developing at an unprecedented speed. However, the trial data produced by the studies on pharmacogenomics is mostly disperse and unstructured, and thus it is very difficult that biologists attempt to access them. If it is possible to develop all kinds of pharmacogenomics databases accessed easily to, the problem can be effectively solved. Therefore, we established the Chinese Pharmacogenomics Network (CPGxNet).In addition, we evaluate the effect of CYP3A and ABCB1gene polymorphisms on cyclosporine A (CsA) pharmacokinetics in the post-renal transplant recipients by a clinical trial. In the present study, we first compared the results from our clinical trial with the data from Web of Science, and then with the correlated results from the CPGxNet database by a kind of tentative reckoning method to validate the reliability of the CPGxNet report forms data.Our findings are as follows:1. Have developed a completely free CPGxNet database based on the Browse/Server (B/S) structure, and the online site is http://www.cpgxnet.net/. 2. At present, collection information in the CPGxNet included5genes,98single nucleotide polymorphisms (SNP),124kinds of drugs and1145variant records. The update in the database will continue in future.3. The Chinese sample sets and the report form function of the CPGxNet database play an important role in reference for the researchers. The module can help researchers make it clear the current research hot spots on pharmacogenomics in Chinese, which involved in the race, region, size, frequency, phenotype, and research time.4. We compared the results from our trial for126Chinese post-renal transplant recipients with the data including in Web of Science and in the CPGxNet, and determined that the data of the CPGxNet report forms were reliable. Therefore, we draw a conlusion that the CPGxNet database has an important reference value.5. By the single gene analysis, we observed the correlation between CYP3A5*3C/CYP3A4-CYP3A5AA and CsA pharmacokinetics in early post-renal transplant recipients (P＜0.05), and but we did not find that the correlation between CYP3A4*1G, ABCB11236C＞T,2677G>T/A,3435C＞T/CYP3A4-CYP3A5AA, ABCB11236-2677-3435and CsA pharmacokinetics (P>0.05);6. By constructing a multivariate linear regression model, we found that there still existed this correlation between CYP3A5*3C and CsA pharmacokinetics (P＜0.05).