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.