Department of Pharmaceutical Sciences, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Pharmacogenet Genomics. 2013 Jul;23(7):349-54. doi: 10.1097/FPC.0b013e328361fb8d.
An increased slowing of cardiac conduction induced by sodium channel blockers is remarkably observed in carriers of an Asian-specific promoter haplotype [haplotype B (HapB)] of the cardiac sodium channel gene (SCN5A). We investigated the effect of HapB on the therapeutic range for serum flecainide concentration in Asian patients.
We examined the serum concentration and antiarrhythmic efficacy of flecainide, together with the SCN5A promoter haplotype, in 146 patients with supraventricular tachyarrhythmias. Trough serum flecainide concentrations were determined by HPLC. The antiarrhythmic efficacy of flecainide was assessed for at least 2 months through examination of symptomatology, ECG, and Holter monitoring.
The serum flecainide concentration did not differ between the wild-type HapA homozygotes and HapB carriers under treatment with the usual dose. A genetic difference in the antiarrhythmic efficacy of flecainide was observed between the HapA homozygotes and HapB carriers at serum flecainide concentrations less than 300 ng/ml (42.9 vs. 68.8%; P=0.022). PR prolongation and QRS widening were observed more commonly among the HapB carriers with serum flecainide concentrations of at least 300 ng/ml than in the HapA homozygotes (PR, 210 ± 25 vs. 195 ± 25 ms; P=0.036; and QRS, 112 ± 10 vs. 105 ± 9 ms; P=0.030).
These findings suggest that the therapeutic range for serum flecainide concentration is lower in HapB carriers than in HapA homozygotes.
在携带亚洲特异性心脏钠离子通道基因（SCN5A）启动子单倍型 B（HapB）的个体中，钠离子通道阻滞剂可显著引起心脏传导阻滞减慢。我们研究了 HapB 对亚洲患者血清氟卡尼浓度治疗范围的影响。
我们检查了 146 例室上性心动过速患者的血清氟卡尼浓度和抗心律失常疗效，以及 SCN5A 启动子单倍型。采用 HPLC 法测定血清氟卡尼浓度。通过检查症状、心电图和动态心电图监测，评估氟卡尼的抗心律失常疗效至少 2 个月。
在常规剂量治疗下，野生型 HapA 纯合子和 HapB 携带者的血清氟卡尼浓度无差异。在血清氟卡尼浓度小于 300ng/ml 时，HapA 纯合子和 HapB 携带者之间氟卡尼的抗心律失常疗效存在遗传差异（42.9% vs. 68.8%；P=0.022）。在血清氟卡尼浓度至少 300ng/ml 的 HapB 携带者中，与 HapA 纯合子相比，PR 延长和 QRS 增宽更为常见（PR：210±25ms 比 195±25ms；P=0.036；QRS：112±10ms 比 105±9ms；P=0.030）。
这些发现表明，与 HapA 纯合子相比，HapB 携带者的血清氟卡尼浓度治疗范围较低。
