CACNA1C基因多态性与钙通道阻滞剂降压疗效的关系  

Impact of CACNA1C polymorphisms on antihypertensive efficacy of calcium channel blocker

作　　者：孙倩[1] 李清贤[1] 宋喜发[2] 郑松贵 晏峰[1] 陈鹏[2] 唐疾飞[2] 牛宇欣 包其郁 张国强[5] 胡云良[1] 

机构地区：[1]温州医学院附属二院检验科,325027 [2]温州医学院附属二院心内科,325027 [3]浙江温州生物信息研究所 [4]温州市鹿城区人民医院 [5]中国科学院北京基因研究所

出　　处：《中华心血管病杂志》2012年第1期3-7,共5页Chinese Journal of Cardiology

基　　金：浙江省科技厅课题（2008C33028）;温州市鹿城区科技局课题（S070116）

摘　　要：目的 探讨L型钙离子通道 alc 哑基基因（CACNAlC）多态性对钙离子通道阻滞剂治疗原发性高血压（EH）患者疗效的影响.方法 对103例EH患者,给单一硝苯地平缓释片进行6周的治疗,采用多重聚合酶链反应方法（Multi-PCR）及基质辅助激光解析-飞行时间质谱分析技术（MLDI-TOF MS）对 rs216008、rs1051375、rs2299661、rs10848683、rs215976进行分型,分析不同基因型间治疗前后血压变化的差值.结果（1）与治疗前相比,硝苯地平缓释片治疗后所有患者平均收缩压和舒张压均出现明显下降（P＜0.05）.（2）rs2299661的CC型舒张压下降幅度明显高于CG型和GG型[（12.46±7.91）mm Hg（1 mm Hg =0.133 kPa）比（7.22±8.01）mm Hg和（5.93±9.77）mm Hg,P＜0.05].（3）rs216008的CC型收缩压下降幅度明显高于CT型[（20.60±12.35）mm Hg比（13.62±10.21）mm Hg,P＜0.05],但与TT型比较差异无统计学意义.（4）rs1051375、rs10848683、rs215976的各基因型间血压变化差值无统计学意义.结论 CACNAI C rs2299661、rs216008的CC型可能会使硝苯地平缓释片治疗EH患者的疗效具更为突出.Objective To explore the relationship between genetic polymorphisms of CACNA1C that encoded the alc subunit of the L-type calcium channel and the efficacy of calcium channel blocker （CCB,Nifedipine extended release tablet/20 mg/d）in essential hypertension（EH）patients of Han Chinese in Wenzhou.Methods For the enrolled 103 EH patients,Multiplex Polymerase Chain Reaction（Muhi PCR）and matrix assisted laser desorption ionization time of flight MS（MLD1-TOF MS）were performed to detect their genotypes（rs216008,rs1051375,rs2299661,rs10848683,rs215976）,blood pressure（BP）after CCB monotherapy was compared among patients with different genotypes.Results（1）Blood pressure was significantly reduced in all patients post CCB（P 〈 0.05 vs.pre-CCB）.（2）Diastolic blood pressure reduction was more significant in subjects with rs2299661 C/C genotype（wild genotype）than in subjects with rs2299661C/G and rs2299661G/G genotype（mutational genotype）[（12.46 ± 7.91）mm Hg （1 mm Hg=0.133 kPa）vs.（7.22±8.01）mm Hgand（5.93 ± 9.77）mm Hg,P〈0.05].（3）Systolic blood pressure reduction was more significant in subjects with rs216008 C/C genotype（wild genotype）than in subjects with rs216008 C/T genotype（mutational genotype）[（20.60 ± 12.35）mm Hg vs.（13.62 ±10.21）mm Hg,P 〈0.05].（4）Blood pressure reduction was similar between subjects with genotype of rs1051375,rs10848683 and rs215976.Conclusion EH patients with wild genotype of rs2299661 and rs216008 in CACNA1 C are more likely to be responders of CCB monotherapy.

关 键 词：高血压 多态性 单核苷酸 钙通道阻滞药 

分 类 号：R544.1[医药卫生—心血管疾病]