| Objective To study the variation rate of CYP2D6 and CYP3A5 genes and the frequency of allele distribution in patients with hypertension in alpine regions,improve the gene pool of CYP2D6 and CYP3A5 in alpine regions,and explore the relationship between the polymorphism of CYP2D6 gene in alpine regions and metoprolol and CYP3A5 gene polymorphism and amlodipine metabolism,so as to provide an effective theoretical basis for individualized precise treatment.Methods The genotypes of CYP2D6 and CYP3A5 were detected in 980 patients with essential hypertension who visited the first affiliated hospital of jiamusi university in the eastern part of heilongjiang province.100 healthy patients who underwent physical examination in the first affiliated hospital of jiamusi university in eastern heilongjiang province were randomly selected for the detection of CYP2D6 and CYP3A5 genotypes as the control group.Age,gender,place of residence,time of residence and other relevant information of the participants were collected and analyzed to analyze the differences in mutation rate and allele distribution frequency of CYP2D6 and CYP3A5 genes between the experimental group and the control group.The results were compared and analyzed with the results of related gene distribution frequency detection reported in other literatures in non-alpine regions to explore the variation rate of CYP2D6 and CYP3A5 genes and the frequency characteristics of allele distribution in patients with essential hypertension in alpine regions and the differences between them and those in non-alpine regions.80 patients with essential hypertension were randomly selected as the CYP2D6 blood concentration group(group A)and given metoprolol sustained-release tablets on an empty stomach every morning at 47.5mg.Peripheral blood was collected 2 hours after taking the drug in the morning of the 8th day for blood concentration and genotype detection of CYP2D6.Then,80 patients with essential hypertension were randomly selected as the CYP3A5 blood concentration group(group B).On the morning of the 8th day,peripheral blood was collected 6 hours after taking the drug,and the blood concentration and CYP3A5 genotype were detected.The relationship between CYP2D6 gene polymorphism and metoprolol drug metabolism and the relationship between CYP3A5 gene polymorphism and amlodipine benzenesulfonate drug metabolism was analyzed by means of variance analysis and T test.Results A total of 980 patients with essential hypertension were included in the experimental group,including 482 patients in the CYP2D6 group and 498 patients in the CYP3A5 group.Healthy control group: 100 cases.The gene distribution frequencies of CYP2D6 and CYP3A5 in healthy groups were consistent with hardy-weinberg law.1.(1)characteristics of CYP2D6 genotype distribution frequency in patients with essential hypertension(482 cases): CC(123 cases)25.5%,CT(164 cases)34.0%,and TT(195 cases)40.5%.The frequency of allele C was 42.5%.The frequency of allele T is 57.5%.Distribution frequency of CYP2D6 gene in healthy group(100 cases): CC(23 cases)23.0%,CT(44 cases)44.0%,TT(33 cases)33.0%.The frequency of allele C was: 45.0%.The frequency of allele T is 55.0%.There was no statistically significant difference in genotype distribution frequency between the CYP2D6 experimental group and the healthy control group(P=0.158),and there was no statistical difference in allele distribution frequency(P=0.521).(2)distribution frequency characteristics of CYP3A5 genotypes in patients with essential hypertension(498 cases): AA(44 cases)8.8%,AG(168 cases)33.7%,GG(286 cases)57.4%.The frequency of allele G was 74.3%.The frequency of allele A was 25.7%.CYP3A5 gene distribution frequency in healthy control group(100 cases): AA(9 cases)9.0%,AG(23 cases)23.0%,GG(68 cases)68.0%.The frequency of allele A was 20.5%.The frequency of allele G was 79.5%.There was no statistical significance in the genotype distribution frequency between the CYP3A5 experimental group and the healthy control group(P=0.101),nor in the allele distribution frequency(P=0.120).2.(1)the distribution frequency of CYP2D6 genotypes was statistically significant(P = 0.001)and the distribution frequency of alleles was not statistically significant(P = 0.980)in comparison with the patients with essential hypertension in alpine regions and in guizhou regions reported in 2019.Compared with the patients with essential hypertension reported in loudi and xiangtan regions of hunan province in 2007,the CYP2D6 genotype and allele frequency were statistically significant(P < 0.001).Compared with patients with essential hypertension reported in Beijing in 2010,the genotype frequency of CYP2D6 was statistically different(P = 0.008),and the allele frequency was statistically significant(P = 0.003).(2)the distribution frequency of CYP3A5 genotype was statistically significant(P < 0.001)and the distribution frequency of allele was statistically significant(P = 0.001)in comparison with the patients with essential hypertension in cold regions and in hunan region reported in 2010.Compared with the patients with essential hypertension in nanchong,sichuan,who were reported in 2017,the gene distribution frequency was statistically significant(P = 0.013),and the allele distribution frequency was statistically significant(P = 0.011).3.(1)standard blood concentration of metoprolol in group A: the standard blood concentration of patients in CC group was 27.03±12.27ng/ml,that of patients in CT group was 22.85±9.26ng/ml,and that of patients in TT group was 60.19±15.01ng/ml.CYP2D6 genome in the standard of three genotypes between blood drug concentration significantly(P < 0.001),respectively the two further two genes type standard blood concentrations of contrast,comparison between CC and CT groups,statistically insignificant(P = 0.318),between CC and the TT group comparison,TT and CT comparison between groups,were statistically significant(P < 0.001).(2)the standard blood concentration of amlodippine besylate in group B was 5.25±1.46ng/ml in group AA,12.11±1.84ng/ml in group GA,and 14.87±2.18ng/ml in group GG.CYP3A5 genome three genotypes of patients in the differences between the blood drug concentration,have significant statistical significance(P < 0.001),respectively the two further two genes type standard blood concentrations of contrast,AA and GA,AA and GG,GA with two two groups of genotype GG standards comparison between blood drug concentration,had statistical significance(P < 0.001).Conclusions 1.There was no difference in the mutation rates of CYP2D6 and CYP3A5 genes between patients with essential hypertension in alpine regions and healthy patients.2.The mutation rate and allele distribution frequency of CYP2D6 and CYP3A5 genes in patients with essential hypertension in alpine regions were different from those in non-alpine regions.3.Different genotypes of CYP2D6 and CYP3A5 in patients with essential hypertension in alpine regions have differences in drug metabolism,requiring individualized medication. |
