The SLC22A2 Genepolymorphisms And Effect Of Rs316019 Mutation On Pharmacokinetics And Pharmacodynamics Of Metformin In Uygur

Objective:To investigate the distribution of three single nucleotide polymorphisms（SNPs）alleles and genotype frequencies of SLC22A2,to further explore the effect of rs316019 C→A mutation on pharmacokinetic parameters and pharmacodynamics of metformin in Xinjiang Uygur healthy population.Methods:Using SNP shot technique,3 genetic polymorphism of SLC22A2 were genotyped,and subsequent pharmacokinetics and pharmacodynamics test were performed on the site of the mutation>10%（rs316019）.Results:The SNP variants of SLC22A2 was rs11920090、rs662301 and rs316019 respectively,and the frequencies of the minimum alleles was 9.1%、2.4%、11.2% respectively.The genotypes distribution was in the Hardy-Weinberg equilibrium（P>0.05）.The C_max、Tmax、T1/2、AUC0-24、AUC0-∞、AUC_0-24-24 of CC were lower than CA;The V/F、CL/F and fe,u of CC were higher than CA,above differences were not statistically significant（P>0.05）.After taking metformin,the fall blood sugar of CC is higher than that of CA,among them indicators include AUC0-0.05、AUC0-3 and a quarter hour blood sugar have statistical significance.There was no significant difference in liver and kidney function after administration.Conclusion:SLC22A2 has a mutation in all three sites among Xinjiang Uygur healthy population,and rs316019 has the highest mutation rate.rs316019 was mutated C→A,and no G→T mutation was found.A mutation reduced the efficacy of metformin hydrochloride and had no significant effect on pharmacokinetic parameters.