The Polymorphism Of CYP2C19 Gene In Guizhou Population And The Effect On Driving Ability After Taking Amitriptyline

Objective: To investigate the distribution of CYP2C19 gene polymorphism in the metabolic key enzyme CYP2C19 in the population of the population of China,and to study the degree of driving damage in the population of CYP2C19 different genotypes in the 10 h after taking amitinine.Methods:1.Optimize the PCR amplification system of CYP2C19 gene by orthogonal optimization comprehensive scoring method.Three hundred and seventy-one unrelated Guizhou populations were selected for amplification after optimization.The AB3500 XL genetic analyzer was used to detect genetic polymorphisms in the CYP2C19*2 and *3 SNP loci.Modified-power state software was used to calculate the allele frequencies.,genotype frequencies and Hardy-Weinberg balance test,calculate non-parent exclusion rate(PE),match probability(Pm),personal recognition rate(DP),heterozygosity(H),polymorphism content(PIC),etc.,statistical analysis of Guizhou population polymorphism distribution characteristics.Through the literature search,the proportion of the metabolic types composed of polymorphisms of CYP2C19*2 and *3 genes in other regions and human races was obtained.The distribution ratio of metabolic types in the Guizhou population was compared with other regions and human races.2.A total of 16 volunteers with different combinations of CYP2C19*2 and *3 genes were selected,except for CYP2C19*2GG/CYP2C19*3AA with only 1 individual and 3 other combinations of various genotypes.Miltline 0.93mg/kg.Six comprehensive capacities for 11 hours from 0h before taking the drug,including connection test,ruler test,stand upright test,drawing test,drowsiness and fatigue scale,for a total of 11 measurements.Using SPSS 22.0 statistical software,using a general linear model to compare statistical differences between groups and time points,and to analyze interaction items between groups and time points to explore whether there are differences in the trend of change between the groups.Results: 1.After optimization,the conditions for the amplification of the 4 L system were as follows: PCR Mix 2.0.2.The frequency of GG,GA and AA genotypes of CYP2C19*2 were 50%,43.22% and 6.94% respectively,and the allele frequency of G and A were 71.61% and 28.39% respectively.The genotypes of GG,GA and AA of CYP2C19*3 were 87.09%,11.94% and 0.97% respectively,and the alleles of G and A were 93.06% and 6.94% respectively.All CYP2C19*17 genotypes were CC.The population genetic parameters of CYP2C19*2 and *3 are as follows: H: 0.435,0.119;PIC: 0.32,0.12;PE: 0.137,0.012;Pm: 0.441,0.773;TPI: 0.89,0.57.The six genotypes formed by mutations at the two sites of CYP2C19*2 and *3 in guizhou population were classified into fast,medium and slow metabolic types according to the metabolic rate,and the distribution frequencies were respectively 43.55%,42.58% and 13.87%.The distribution frequency of CYP2C19 fast,medium and slow was not statistically significant between guizhou population and shenyang,chongqing and other seven regions.There was no statistically significant difference between the distribution frequencies of CYP2C19 fast,medium and slow metabolites in the Chinese population represented by the guizhou population and those in Japan,Thailand and India.Compared with the distribution frequency of CYP2C19 metabolic types in white and black populations,the Asian population represented by guizhou population was statistically significant.3.In each ability test,the time points of the maximum scores of each group are different: the time points of the maximum grasping value of each group of the ruler AF after taking the medicine are: 4h,7h,6h,7h,7h,6 ~8h;fatigue evaluation of the A ~ F genotypes of the maximum time points in order: 5,4 ~ 5h,6h,5h,4h,3h;sleepiness assessment,A ~ F genotypes of the maximum time The points are: 4,4,4,5,4,and 5h;the time points of the maximum values of A to F genotypes in the linkage test are: 3,6,4,5,7,and 6h;The maximum values of A to F are: 8,2,2,2h,2 and 8h.The differences of each group were as follows: there were statistically significant differences between group A and group D,group C and group D,group D and group E in the ruler test(p < 0.05).The difference between group A and group E in the fatigue test was statistically significant(p < 0.05).In the narcolepsy test,the differences between group A and group D,group A and group E were statistically significant(p < 0.05).The differences between group B and group D,group B and group E were statistically significant(p < 0.05).The differences between group C and group D,group C and group E were statistically significant(p < 0.05).In the wire test;The differences between group A and group C,group A and group E were statistically significant(p < 0.05).No difference between the balance groups;In the drawing test,there were statistically significant differences between group A and group C,group A and group D(p < 0.05).Comprehensive evaluation was conducted for each ability.The smaller the area,the greater the impact was compared with the maximum impact time point of each group.The minimum area time points of the drip A~F group are: in 4,6,6,4,7,6h.The minimum area of each successive A~F group is different.The duration of exposure varies from group to group: group A 5h;Group B had 7h,group C,D and F had 8h and group E had 9h.Conclusions: 1.Orthogonal design combined with comprehensive scoring method has the advantages of comprehensive evaluation index,intuitive result analysis,simple design process and objective evaluation method,and is suitable for optimization of DNA amplification conditions.2.The distribution frequency of each metabolic type of CYP2C19*2,*3 genes has no regional differences in China and Asia,but differences exist between Asian races,white races,and black races.3,after taking amitriptyline,fatigue and sleepiness corresponding to the greater impact of alertness and attention,drawing,single leg erection corresponding visual memory and balance force execution ability without statistical differences.4.Within 10 h after taking amitriptyline,there are certain differences in the influence of comprehensive driving ability of different genotypes.5.The constructed comprehensive driving ability assessment method can be used to easily and quickly assess the influence of driving ability after taking drugs.