Distribution Of SLC22A1 Rs683369 In Xinjiang Uygur Male Population And Its Effect On Metformin Pharmacodynamics

Objective:To investigate the distribution of SLC22A1 rs683369 locus polymorphism in Uyghur male population and to compare the differences of distribution among different races and to explore the genetic polymorphism of rs683369 SLC22A1 locus in Uygur male population Effect of metformin pharmacodynamics.Methods:Genotyping of SLC22A1 rs683369(480C> 160Phe> Leu)loci in 276 Uighur male volunteers was performed by SNa Pshot SNP typing and was compared with the genotyping data of different races in NCBI gene pool To compare and analyze the ethnic differences in their distribution,276 subjects were divided into experimental group and control group during the experiment.The experimental group had a family history of diabetes and the control group had no family history of diabetes.According to the aforementioned genotyping results,we selected the healthy volunteers who participated in the genetic polymorphism of metformin in Uygur male subjects with S68229 locus mutation of rs683369,and screened out 23 loci in SLC22A1 rs683369(F160L),CC wild-type homozygotes(n=19)and CG mutant heterozygotes(n=4).The experiment organized 23 subjects,before and after taking metformin were measured at different time points of blood glucose and blood insulin concentrations.Results:There were 195 cases(70.7%),73 cases(26.4%)and 8 cases(2.9%)of CC,CG and GG in rs683369 polymorphism respectively.The frequency of C allele was 83.9% 16.1%,rs683369 locus distribution frequency obey Hardy-Weinberg genetic balance law.The frequency of rs683369 locus in Uighur Xinjiang was significantly different from that of Yoruba,Kenyans and African Americans(P <0.05).rs683369 gene loci in the family history of diabetes and non-family history of diabetes genotype frequency distribution was no significant difference(P> 0.05).There were no significant differences in liver and kidneyfunction indexes and blood glucose at different time points before and after taking metformin between CC wild type homozygote(n=19)and rs683369 CG mutant heterozygous(n=4)in SLC22A1 rs683369 CC group.The difference of Decremental AUC0-3 in the area under the curve of blood sugar-time within 3 hours before and after taking metformin before and after taking CC and CG was-1.89±0.50 mmol·h / L and-2.88±0.53 mmol·h / L,there was a statistically significant difference between the two groups(P=0.004).Conclusion:The rs683369 locus of SLC22A1 locus in the Uyghur male population in Xinjiang obeyed the Hardy-Weinberg law of genetic balance(P>0.05),and had a high mutation rate.This locus showed no significant difference between the family history of diabetes mellitus and nondiabetic Family history of genotype frequency distribution was not statistically significant.The C → G polymorphism of SLC22A1rs683369 gene may affect the pharmacodynamic effect of metformin in Xinjiang Uyghur people,resulting in lower efficacy.