College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University.
College of Pharmacy and Division of Life & Pharmaceutical Sciences, Ewha Womans University.
Pharmacogenet Genomics. 2020 Aug;30(6):124-130. doi: 10.1097/FPC.0000000000000404.
The present prospective follow-up study aimed to evaluate the effects of KCNMB2 gene polymorphisms on ritodrine efficacy and adverse drug events (ADEs) in patients with preterm labor.
A total of 163 preterm labor patients were included in this single-center study. Nine single nucleotide polymorphisms (SNPs) in the KCNMB2 gene (rs10936979, rs7624046, rs7429015, rs7625907, rs6443559, rs9839376, rs9637454, rs11918114, and rs1382045) were assessed. The primary endpoint was time to delivery, and the secondary endpoint was ritodrine-induced ADEs.
Patients with variant homozygotes of two SNPs (rs7624046 and rs9839376), which were in linkage disequilibrium, showed 2.06 [95% confidence interval (CI), 1.14-3.73] and 2.68 (95% CI, 1.16-6.20) times the hazard of time to delivery compared to wild-type allele carriers, respectively. Among demographic characteristics, gestational age at start of drug therapy and modified Bishop score were significant factors for time to delivery. Regarding safety outcomes, patients with variant homozygotes of rs7625907 had fewer ADEs compared to those with other genotypes (odds ratio, 0.32; 95% CI, 0.13-0.83).
This pharmacogenomic study suggests that ritodrine efficacy and ADEs are associated with KCNMB2 gene polymorphisms in patients with preterm labor.
本前瞻性随访研究旨在评估 KCNMB2 基因多态性对早产患者利托君疗效和药物不良事件（ADEs）的影响。
本单中心研究纳入了 163 例早产患者。评估了 KCNMB2 基因（rs10936979、rs7624046、rs7429015、rs7625907、rs6443559、rs9839376、rs9637454、rs11918114 和 rs1382045）中的 9 个单核苷酸多态性（SNP）。主要终点是分娩时间，次要终点是利托君引起的 ADEs。
与野生型等位基因携带者相比，两个连锁不平衡 SNP（rs7624046 和 rs9839376）的变异纯合子患者的分娩时间风险分别增加了 2.06（95%置信区间[CI]，1.14-3.73）和 2.68（95% CI，1.16-6.20）倍。在人口统计学特征中，药物治疗开始时的孕周和改良 Bishop 评分是分娩时间的重要因素。关于安全性结果，与其他基因型相比，rs7625907 的变异纯合子患者的 ADEs 更少（比值比，0.32；95% CI，0.13-0.83）。
这项药物基因组学研究表明，早产患者的利托君疗效和 ADEs 与 KCNMB2 基因多态性有关。
