Association Study Between Genetic Polymorphisms Of KCNH2,KCNMB1,KCNJ11 And Antihypertensive Efficacy Of Amlodipine Besylate

Objective: To investigate the effect of KCNH2,KCNMB1 and KCNJ11 genetic polymorphisms on the antihypertensive efficacy of amlodipine besylate in patients with mild to moderate essential hypertension.Methods: Based on the real world,a total of 121 patients with mild to moderate essential hypertension were treated with 5 mg amlodipine besylate everyday for four weeks.The patients were regularly followed up and the clinical data of the patients were collected.The KCNH2 gene rs1137617 locus,KCNMB1 gene rs11739136 locus and KCNJ11 gene rs5219 locus were genotyped by polymerase chain reaction-restriction fragment length polymorphism technique,in order to understand their characteristics of genotypic distribution in hypertensive population.The relationship between different genotypes and antihypertensive efficacy of amlodipine besylate was analyzed.Results: 1.The frequencies of KCNH2-rs1137617,KCNMB1-rs11739136 and KCNJ11-rs5219 genotypic distribution accord with the Hardy-Weinberg equilibrium.2.After four weeks of treatment with amlodipine besylate alone,the mean systolic blood pressure and mean diastolic blood pressure in patients with essential hypertension were significantly lower than those before treatment(P<0.05).3.After treatment with amlodipine besylate monotherapy in hypertensive patients carrying different KCNH2 genotypes for four weeks,the CT/TT genotypic carriers were significantly better than the CC genotypic carriers in the reduction of diastolic blood pressure,and the difference was of statistical significance(P=0.024).There was no statistically significant difference in the reduction of systolic blood pressure between carriers of different genotypes(P=0.053).After treatment with hypertensive patients carrying different KCNMB1 genotypes,CT/TT genotypic carriers were significantly better than CC genotypic carriers in terms of systolic blood pressure and diastolic blood pressure reduction,and the differences were of statistical significance(P<0.05).There was no statistically significant difference in the reduction of systolic blood pressure and diastolic blood pressure between GG and GA/AA genotype in hypertensive patients with different KCNJ11 genotypes(P>0.05).4.After four weeks of treatment with amlodipine besylate alone,the difference in total effective rate of the reduction of blood pressure between different genotypes of KCNH2-rs1137617,KCNMB1-rs11739136 and KCNJ11-rs5219 was not of statistical significance(P>0.05).The difference in the composition ratio of antihypertensive effect between different genotypes of the three loci was of statistical significance(P<0.05).Conclusions: 1.The KCNH2-rs1137617 genetic polymorphism is associated with the antihypertensive efficacy of amlodipine besylate in the treatment of essential hypertension.The effect of amlodipine besylate on the response to the reduction of diastolic blood pressure in patients with essential hypertension carrying the KCNH2-rs1137617 CT/TT genotype is greater than that of CC genotypic carriers,whereas amlodipine besylate has no effect on the response to the reduction of systolic blood pressure among carriers of different genotypes.2.The KCNMB1-rs11739136 genetic polymorphism is related to the antihypertensive efficacy of amlodipine besylate in the treatment of essential hypertension.The effects of amlodipine besylate on the response to the reduction of systolic blood pressure and diastolic blood pressure in patients with essential hypertension carrying the KCNMB1-rs11739136 CT/TT genotype were significantly greater than those of CC genotypic carriers.3.The association between KCNJ11-rs5219 genetic polymorphism and antihypertensive efficacy of amlodipine besylate in the treatment of essential hypertension was not found.