Ugt And The Mitiglinide Pharmacokinetic And Aldh2 And Nitrates Efficacy Of School Association Study

Background:UGT (ur idine 5'-diphosphate glucuronosyltransferase) is an important two-phase metabolic enzymes, UGT1A3 and UGT2B7 are reported to metabolize Mitiglinide used in diabetes in the literature, and it is gene polymorphism, different genotypes showed different metabolic activity to substrate.But the research for different genotypes activity of UGT is limited to recombinant enzyme experimental in vitro, has not addressed whether it have impact in vivo. From this view, we study the correlation between UGT1A3,UGT2B7 genetic polymorphism and significant individual different pharmacokinetics of Mitiglinide.Objective:To detect the effect of phaseâ…¡metabolic enzymes UGT1A3 and UGT2B7 genetic polymorphism on individual's differences of Mitiglinide pharmacokinetic(PK) in chinese,and to provide a basis for the clinical rational usage of the drug.Method:Use pyrosequencing to detect the UGT1A3 and UGT2B7 SNPs of 42 pepole,then select 12 health volunteers (8 mens and 4 womens),and use HPLC-MS to detect their single and multiple oral Mitiglinide blood concentration,then acquire the pharmacokinetic parameters respectively;,and devide groups according to the different genotypes. The way of comparision of PK parameters between groups(or among groups) is ANOVA or two independent-samples t test.p<0.05 is considered statistically significant.Result:From the value of the volunteers Mitiglinide plasma concentration and PK parameters, there are great individual difference in PK,and it have no relationship with UGT1A3 and UGT2B7 genetic polymorphism by statistical analysis for single oral Mitiglinide, but is related with UGT1A3 genetic polymorphism for multiple oral Mitiglinide. The comparision of the enzymes activity to metablize Mitiglinide is UGT1A3*1/*3>UGT1A3*1/*2> UGT1A3*1/*5.Conclusion:Phaseâ…¡metabolic enzymes UGT1A3 gennetic polymorphism have impact on individual PK difference of Mitiglinide, but UGT2B7 have not. Objective:To detect the correlation between the ALDH2 gene polymorphism in patients with coronary heart disease and nitrate (nitroglycerin and isosorbide dinitrate) efficaoy, and to provide a foundational theory for the clinical rational usage of the drug,Method:Select 57 patients of coronary heart disease from 2009.5 to 2009.12 in our hospital and make the corresponding test inclusion criteria and exclusion criteria, record patient's clinical information, including the age, sex, weight, medical history, etc, and detect their genotype. Evaluate the efficacy of nitrates according to three aspects:clinical efficacy, ECG, cardiac function, first, divide two groups based on the genotype ALDH2*1/*1 and ALDH2*1/*2 ALDH2*2/*2. and then to analysis wether there are differences between the dosage of the two groups. again, divide two groups:effective group and ineffective group based on the three aspects above in the situation of common dosage and then analysis whether there are genotype distribution differences between the two groups. The third, to analysis whether there are different distribution of genotypes between the drinking red and not drinking red.Results:From the clinical data we can learn that:there are no difference between the two groups of genotypes about age,sex,cardiovascular disease risk factors,medication history,etc. In the stable situation of drug treatment, there is significant differences between the two groups'dosage of nitroglycerin per week, but differences do not exist between the daily contents of isosorbide dinitrate. In the situation of conventional dosage of the drug nitroglycerin, there is statistically significant between the distribution of genotype in the two groups(effective group and ineffective group).And the correlation exist between ALDH2 gene polymorphism and drinking red.Conclusion:The patients with Coronary heart disease can use their nitrates based on their genotype, in order to avoid delays in treatment time because of lower dosage, reduce side effects and improve therapeutic effect. There is a certain correlation between the genotypes and drinking red, we can also learn their genetic information indirectly.