Genetic Polymorphisms of L-Type Calcium Channel α1C and α1D Subunit Genes are Associated With Sensitivity to the Antihypertensive Effects of L-Type Dihydropyridine Calcium-Channel Blockers
Genetic Polymorphisms of L-Type Calcium Channel α1C and α1D Subunit Genes are Associated With Sensitivity to the Antihypertensive Effects of L-Type Dihydropyridine Calcium-Channel Blockers
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DOI：
10.1253/circj.cj-08-0761
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发表时间：
2009-04-01
影响因子：
3.3
通讯作者：
Kawano, Yuhei
中科院分区：
文献类型：
--
作者：
Kamide, Kei;Yang, Jin;Kawano, Yuhei
背景：L类二氢吡啶类钙通道阻滞剂对血压的影响因个体不同而异。方法与结果：对161例服用二氢吡啶类钙通道阻滞剂的高血压患者进行药物基因组学分析，研究钙通道α1C和α1D亚单位基因CACNA1C和CACNA1D基因多态性是否与二氢吡啶类钙通道阻滞剂的降压作用有关。应答者定义为经dCCBS治疗后，收缩压(SBP)下降>20 mm Hg或舒张压(DBP)下降>10 mm Hg者。从公共数据库中选择CACNA1C的11个序列多态和CACNA1D的5个常见多态进行基因分型。CACNA1D基因rs312481G>；A和rs3774426C>；T，CACNA1C527974G>；A基因多态频率差异有统计学意义，这些单核苷酸多态(SNPs)等位基因间SBP和DBP差异有统计学意义。结论：CACNA1D或CACNA1C中的3个SNP是导致高血压患者对L类dCCBS降压作用敏感的遗传多态。通过对这些多态的评估，可以预测L型双氯联苯的降压作用。(保监会J 2009；73：732-740)
Background: The response of blood pressure (BP) to L-type dihydropyridine calcium-channel blockers (dCCBs) differs among individuals.Methods and Results: A pharmacogenomic analysis was undertaken in 161 patients with essential hypertension who were treated with dCCBs to study whether genetic polymorphisms of the calcium channel alpha 1C and alpha 1D subunit genes, CACNA1C and CACNA1D, are associated with the antihypertensive effects of dCCBs. Responders were defined as those in whom systolic BP (SBP) was lowered by more than 20mmHg or diastolic BP (DBP) was lowered by more than 10 mmHg after treatment with dCCBs. Eleven sequence-proven polymorphisms of CACNA1C and 5 common polymorphisms of CACNA1D chosen from a public database were subjected to genotypic analysis. The comparison of polymorphism prevalence between responders and nonresponders showed significant differences in CACNA1D rs312481G > A and rs3774426C > T, and in CACNA1C 527974G > A. There were significant differences in SBP or DBP between alleles in these single nucleotide polymorphisms (SNPs). A much more significant reduction in BP was observed for the combined presence of these SNPs.Conclusions: Three SNPs in CACNA1D or CACNA1C are genetic polymorphisms conferring sensitivity to the antihypertensive effects of L-type dCCBs in patients with hypertension. The BP reduction by L-type dCCBs might be predicted by evaluating these polymorphisms. (Circ J 2009; 73: 732-740)