Correlation Study Between Hypertension Medication Gene And Clinical Efficacy

Objective: To investigate the distribution of seven hypertension drug-related gene polymorphisms among Han Chinese patients with essential hypertension（EH）,Hubei Province;and to investigate the association between CYP3A5,CYP2C9 and AGTR1 genotypes and the efficacy of calcium channel blocker（CCB）and angiotensin II receptor blocker（ARB）drugs in EH patients.To provide relevant support for individualised treatment.Methods: General data（gender,age,weight,past medical history,medication history,family history,baseline blood pressure,etc.）were collected from 261 patients with essential hypertension who attended the outpatient clinic of Hubei Provincial Hospital of Traditional Chinese Medicine from September 2020 to June 2021,and venous blood samples were collected from each patient for routine blood tests,liver and kidney functions and urine samples for routine urine tests.After 4 weeks of clinical follow-up,7genotypes of the 5 classes of hypertensive drugs recommended by WHO were detected by PCR-fusion genetic testing.The frequency distribution of each gene in EH patients was analysed,and the distribution of genotypes in different gender groups and with or without genetic family history was analysed using SPSS23.0 statistical software.At the same time,72 cases of hypertensive patients taking oral antihypertensive drugs of the CCB class and 46 cases taking oral antihypertensive drugs of the ARB class were selected to investigate the correlation between their clinical efficacy and CYP3A5,CYP2C9 and AGTR1 genotypes.Results:（1）The frequencies of CYP3A5*3,CYP2C9*3,AGTR1（1166A>C）,NPPA（T2238C）,CYP2D6*10,ADRB1（1165G>C）,and ACE（I/D）genetic mutation in 261 patients with EH were respectively 74.52%,4.79%,6.70%,0.77%,55.75%,74.14%,and 33.72%.（2）The mutation frequency distribution of the seven hypertension drug-associated loci was not significantly correlated by sex or family history（P>0.05）,consistent with Hardy-Weinberg equilibrium.（3）The frequency distribution of genotyping of hypertension drug-related genetic mutation differed across geographic regions.（4）The higher mutation frequency of CYP3A5*3,CYP2D6*10 and ADRB1（1165G>C）in patients with EH,Hubei,suggested higher sensitivity to calcium channel blockers and β-blockers;the lower mutation frequency of NPPA（T2238C）suggested diuretics sensitivity was low.（5）In 72 EH patients taking oral CCB class drugs,the results showed that the distribution of CYP2C9 and AGTR1 gene polymorphisms did not correlate with the effectiveness of clinical efficacy of CCB class antihypertensive drugs,P>0.05;while CYP3A5*1/*3 genotype improved efficacy 8.973-fold compared with *1/*1genotype（P= 0.012,OR = 8.973,95% CI:0.492-3.896）and 1.379 times more clinically effective in *3/*3 patients than in *1/*1 patients（P= 0.554,OR =1.379,95% CI:-0.743-1.386）.（6）In 46 EH patients taking oral ARB classes,the results showed an association between CYP3A5*3 locus typing frequency distribution and the degree of effectiveness of clinical efficacy of ARB class antihypertensive drugs,with CYP3A5*1/*3 genotypes being 7.025-fold more effective than *1/*1 genotypes（P= 0.029,OR = 7.025,95% CI1.223 to40.360）The clinical efficacy of *3/*3 patients was 6.09 times higher than that of *1/*1 patients（P= 0.026,OR = 6.090,95% CI 1.242-29.866）;while there was no effect on CYP2C9 in both the apparent and effective groups of ARB class antihypertensive drugs compared to the ineffective group（P values 0.769 and 0.974,respectively）,and no effect on AGTR1（P > 0.05）.Conclusion: The distribution of genotypes in 261 patients with EH was not significantly correlated with gender and family history;among the seven genotypes,the higher frequency of mutations in CYP3A5*3,CYP2D6*10 and ADRB1（1165G>C）suggested a higher sensitivity to calcium channel blockers and β-blockers;the lower frequency of mutations in NPPA（T2238C）suggested a lower sensitivity to diuretics;Gene polymorphisms of CYP3A5 were associated with the efficacy of CCB and ARB antihypertensive drugs,while no gene polymorphisms of AGTR1 and CYP2C9 were observed to be associated with the efficacy of CCB and ARB antihypertensive drugs.