氨氯地平降压疗效与L型钙离子通道α1C亚基的基因多态性的关系  

Relationship of the genetic polymorphisms of L-type calcium channel α 1C gene and efficacy of amlodipine in the treatment of essential hypertension

作　　者：景林德[1] 刘玉清[1] 刘红[1] 贾友宏[1] 王文[2] 马丽媛[2] 黄建凤[3] 张进虎[4] 李一石[1] 

机构地区：[1]北京协和医学院、中国医学科学院阜外心血管病医院卫生部心血管药物临床研究重点实验室,北京100037 [2]北京协和医学院、中国医学科学院阜外心血管病医院卫生部心血管病防治研究中心,北京100037 [3]北京协和医学院、中国医学科学院阜外心血管病医院高血压诊治中心,北京100037 [4]航空总医院,北京100012

出　　处：《中国临床药理学杂志》2012年第1期8-12,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家“重大新药创制”科技重大专项基金资助项目(2008ZX09312-018);国家“十一五”科技支撑计划课题基金资助项目(2006BAI01A03)

摘　　要：目的研究氨氯地平的降压疗效与L型钙离子通道α1C亚基的基因(CACNA1C)单核苷酸多态性(SNPs)间的关联。方法纳入181例服用氨氯地平的原发性高血压患者,用PCR-直接测序法,对CACNA1C基因单核苷酸多态性(SNPs)rs1051375、rs2238032、rs7311382、rs2239050、rs2239127、rs2239128和rs2239129等位点进行基因分型;用多元线性回归方法,分析SNPs位点基因型与氨氯地平降压疗效间的关系。结果调整基线血压、体质量指数、血脂异常、性别和年龄的影响后,rs2238032G/T位点基因多态性与氨氯地平的降压疗效明显相关(△SBP:P=0.02;△DBP:P=0.01);rs1051375A/G、rs7311382C/T、rs2239050G/C、rs2239127C/T、rs2239128C/T和rs2239129C/T位点虽均显示出基因型间氨氯地平降压疗效的差异,但均无统计学意义(P>0.05)。结论 CAC-NA1C基因rs2238032位点基因多态性与原发性高血压患者服用氨氯地平的降压效果明显相关。Objective To study association between genetic polymorphisms of L-type calcium channel alpha subunit 1C gene（CACNA1C） and efficacy of amlodipine in the treatment of hypertension.Methods A pharmacogenetic analysis was performed on 181 Chinese individuals with essential hypertension who were treated with amlodipine based antihypertensive drugs.Seven SNPs（rs1051375,rs2238032,rs7311382,rs2239050,rs2239127,rs2239128,rs2239129） in CACNA1C were chosen for genotypic analysis using direct sequencing method.Multiple linear regression was used to association analysis between genetic polymorphisms and efficacy of amlodipine.Results After adjustments of the influence of confounding factors on blood pressure,the comparison of 4th week′s △SBP and △DBP over genotypes of these single nucleotide polymorphisms showed that rs2238032G/T had a more significant association with BP reduction after treatments（△SBP：P=0.02;△DBP：P=0.01）.Both SBP and DBP were significantly decreased in patients with TT＋GT carrier in rs2238032 G/T when compared with patients with GG carrier.And rs2239050C/G,rs7311382C/T,rs2239127C/T,rs2239128C/T,rs2239129C/T,rs1051375A/G showed a significant difference in BP reduction over genotypes respectively.Conclusion SNPs rs2238032 in CACNA1C are associated with efficacy of amodipine in the treatment of essential hypertension.

关 键 词：CACNAIC基因 单核苷酸多态性 高血压 氨氯地平 

分 类 号：R544.1[医药卫生—心血管疾病] R972.4[医药卫生—内科学]