The aim of the study is to identify the effect of UDP-glucuronosyltransferase (UGT) genetic polymorphism on the interindividual variability in mitiglinide pharmacokinetics (PK) in Chinese. PK and genetic data were obtained from 42 healthy Chinese volunteers (Han ethnic group) treated with single-dose and multiple-dose oral mitiglinide using liquid chromatography/mass spectrometry and DNA sequencing technologies. And the result showed there were great interindividual variabilities in main PK parameters (AUC, Cmax and CL/F) for multiple oral mitiglinide. The enzyme activity of the carriers of UGT1A3 *2/*4 or UGT2B7-1 T/T was stronger than that of the carriers of other genotypes. These results demonstrate that UGT1A3 and UGT2B7-1 genetic polymorphism may have a significant impact on interindividual variability in the PK of mitiglinide in Chinese.

Objective To establish a pyrosequencing-based method to detect UGT1A3 and UGT2B7 gene polymorphism in Chinese population.Methods Biotin-labeled primers,amplification of PCR,separation of Beads,and preparation of UGT1A3 and UGT2B7 pyrosequencing single-stranded template of mutational sites were done to determine the allelic frequency of the UGT1A3 and UGT2B7 mutant in 233 Chinese subjects by pyrosequencing apparatus.Results There were 9 genetypes of the allele of UGT1A3:UGT1A3*1*1,UGT1A3*1*2,UGT1A3*1*3,UGT1A3*1*4,UGT1A3*1*5,UGT1A3*2*3,UGT1A3*2*4,UGT1A3*3*3,and UGT1A3*3*5 respectively.There were 3 genetypes based on the presence of UGT2B7-1: genetypes G/G,G/T,and T/T;and 3 genetypes of the allele of UGT2B7-2: C/C,C/T,and T/T.Conclusion The frequency of the UGT1A3 and UGT2B7 mutant allele is high in Chinese population.

Objective:To determine the effect of genetic polymorphisms of the metabolic enzyme UGT on individual differences of mitiglinide pharmacokinetic(PK) in Chinese,and provide a basis for the clinical rational usage of the drug.Methods:Health volunteers took single and multiple oral doses of mitiglinide.HPLC-MS was used to detect blood concentration of mitiglinide,pyrosequencing was used to detect the SNPs of UGT1A3 and UGT2B7.Then,the pharmacokinetic parameters were acquired respectively,and the volunteers were divided into groups according to the different genotypes.The PK parameters between groups(or among groups) were compared using ANOVA or two independent-samples t test;P0.05 was considered statistically significant.Results:From the values of plasma mitiglinide concentrations and PK parameters(AUC,Cmax,CL),there were great individual differences in PK.The differences did not relate to UGT1A3 and UGT2B7 genetic polymorphisms as analyzed by statistical analysis for single oral dose of mitiglinide,but relate to UGT1A3 and UGT2B7 genetic polymorphisms for multiple doses.The order of enzymes activities to metabolize mitiglinide was UGT1A3*2/*4UGT1A3*1/*3UGT1A3*1/*1UGT1A3*1/*2UGT1A3*1/*5,and the genetic polymorphism of UGT2B7-1 was T/TG/TG/G.Conclusion:The genetic polymorphisms of phase II metabolic enzymes,UGT1A3 and UGT2B7-1 but not UGT2B7-2,impact individual PK difference of mitiglinide.

Objective To investigate the correlation between G487A variant of aldehyde dehydrogenase-2(ALDH2)gene polymorphisms and hypertension in patients with coronary heart disease.Methods Fifty-seven patients with coronary heart disease were enrolled in this study.The genotypes of ALDH2 were determined by pyrophosphate sequencing.The patients were divided into two groups according to the genotypes,namely GG group(n=43)and GA/AA group(n=14).The incidence of hypertension and the risk factors of cardiovascular disease and systolic/diastolic/pulse blood pressure,on treatment were assessed.Results The hypertension incidence of GA/AA group(85.7%)was significantly higher than that of GG-type group(53.5%),in the statistically significant manner(P= 0.05).The difference in systolic and diastolic blood pressure between the two groups were not statistically significant(P0.05),while the pulse pressure of GA/AA groupwas significantly higher than that of GG group,in the statistically significant manner(P0.01).Conclusion G487A variant of aldehyde dehydrogenase-2(ALDH2)gene polymorphism might be a risk factor for hypertension,one of the mechanisms related to endogenous NO synthesis.In addition,its effect on nitroglycerin might increase the pulse pressure in old patients with coronary heart disease.