Correlation Between Single Nucleotide Polymorphism Of CACNA1C And Levamlodipine And Establishment Of Snp Detection Platform

Objective:To explore the correlation between single nucleotide polymorphisms of CACNA1C(rs2239128,rs2239050 and rs2238032)and the levamlodipine,and to establish a convenient and feasible SNP detection platform.Method:From June 2018 to December 2018,89 eligible patients with mild to moderate essential hypertension(SBP 140-179 mmHg and/or DBP 90-109 mmHg)were enrolled.All patients with essential hypertension were diagnosed in accordance with the “Revised Chinese Guidelines for the Prevention and Treatment of Hypertension 2018”,and all patients signed the informed consent.All patients were treated with levamlodipine 2.5 mg/tablet/QD(Trade name: Shi Huida)for 4 weeks after drug elution for 2 weeks.No other drugs affecting blood pressure should be used during the treatment.The basic blood pressure,blood pressure after 4 weeks of treatment,height,weight,smoking history,drinking history,diabetes history and other related clinical data were collected,and the related indicators of liver and kidney function and lipids were determined.To evaluate the antihypertensive effect according to the Guiding Principles for Clinical Research of Cardiovascular Drugs.Before treatment,2 ml venous blood was used in EDTA anticoagulant tube to extract genomic DNA.qPCR was used to genotype the SNP of the target gene,and DNA sequencing was used to verify the research site.The correlation between different genotypes and the antihypertensive effect of levamlodipine was analyzed,and the results of qPCR and gene sequencing were compared.Data analysis using SPSS22.0 software package.Results:1.compared with before treatment,systolic blood pressure and diastolic blood pressure of all the patients treated with levamlodipine decreased.2.after 4 weeks of single-drug treatment with levamlodipine tablets,among the 89 patients with mild and moderate essential hypertension,60 patients(67.42%)were in the effective group and 29 patients(32.58%)were in the ineffective group,with an overall effective rate of 67.42%.The systolic and diastolic blood pressure decreases in the effective and ineffective groups were respectively(? SBP 23.37±11.57 mmHg,13.48±6.22 mmHg ? DBP 12.75±7.51 mmHg,5.52±2.42 mmHg,p < 0.01).There were no significant differences in general clinical data and biochemical indexes such as sex,age,heart rate,smoking history,drinking history,BMI,diabetes history,fasting blood sugar,TG,TC,baseline systolic blood pressure and baseline diastolic blood pressure between the two groups.3.After adjustments of the confounding factors(age?smoking?drinking?BMI?fasting blood glucose?TG?LDL-C?baseline SBP?baseline DBP),we found that the genotype of CACNA1 C rs2239128C>T CC vs(CT/TT)was associated with ?DBP(13.94±8.03 mmHg,7.93±5.50 mmHg,B=-6.844,p<0.001,respectively),and there was no significant correlation with ?SBP(22±10.56 mmHg,18.94±11.41 mmHg,B=-1.992,p=0.426);the genotype of CACNA1 C rs2239050G>C GG vs(GC/CC)was associated with ?SBP(21.46±11.86 mmHg,16.96±8.48 mmHg,B=-5.572,p=0.039,respectively),and there was significant correlation with ?DBP(11.25±7.48 mmHg,7.96±5.99 mmHg,B=-3.432,p=0.046);the genotype of CACNA1 C rs2238032T>G TT vs(TG/GG)was associated with ?SBP(21.15±11.76 mmHg,16.90±8.16 mmHg,B=-6.105,p=0.037,respectively),and there was significant correlation with ?DBP(10.43±7.33 mmHg,9.86±6.93 mmHg,B=3.263,p=0.048,respectively).4.In the effective group of 60 cases,three SNP mutations occurred in 0 cases,two SNP mutations occurred in 6 cases(10%),one SNP mutation occurred in 37 cases(61.67%)and no mutation occurred in 17 cases(28.33%);in the ineffective group of 29 cases,three SNP mutations occurred in 2 cases(6.90%),two SNP mutations occurred in 20 cases(68.97%),one SNP mutation occurred in 7 cases(24.13%)and no mutation occurred in 0 cases.In the effective group,6 cases(10%)had more than two SNP mutations,22 cases(75.87%)had more than two SNP mutations in the ineffective group,and the patients with more than two SNP mutations in the ineffective group were significantly higher than those in the effective group,the difference was statistically significant(p < 0.01).5.QPCR was used to detect SNP genotypes,and the results were in good agreement with the sequencing results.Conclusion:1.The effective rate of levamlodipine in patients with mild to moderate essential hypertension was 67.42%.2.The SNP of CACNA1 C gene is related to the clinical antihypertensive effect of levamlodipine.The hypotensive effect of CACNA1 C rs2239128C > T CC genotype on levamlodipine was better than that of T allele carriers;the hypotensive effect of rs2239050 G > C GG genotype on amlodipine was better than that of C allele carriers;and the hypotensive effect of rs2238032 T > G TT genotype on levamlodipine was better than that of G allele carriers.3.SNP mutation detection can be used to guide the clinical use of antihypertensive drugs.4.The qPCR detection platform established in this experiment can be used to detect SNP mutation sites.