Chung Jee Eun, Choi Soo An, Hwang Han Sung, Park Jin Young, Lee Kyung Eun, Yee Jeong, Kim Young Ju, Gwak Hye Sun
School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do, 16419, Korea.
College of Pharmacy, Korea University, Sejong-Si, 30019, Korea.
BMC Genet. 2017 Nov 13;18(1):96. doi: 10.1186/s12863-017-0565-8.
Ritodrine, a tocolytic β2-agonist, has been used extensively in Europe and Asia despite its safety concerns. This study was designed to identify associations between β2-adrenergic receptor (ADRB2) polymorphisms and adverse drug events (ADEs) in patients with preterm labor treated with ritodrine.
This follow-up study was prospectively conducted at Ewha Womans University Mokdong Hospital in Korea. Five single nucleotide polymorphisms (SNPs) of the ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718, and rs1042719) were analyzed in 186 pregnant women with preterm labor. Patients with the AA genotype of rs1042717 had significantly lower incidence of ADEs compared to those with the G allele (p = 0.009). In multivariate analysis, one of the predictors of ADEs was the maximum infusion rate of ritodrine (AOR 4.47, 95% CI 1.31-15.25). Rs1042719 was also a significant factor for ritodrine-induced ADEs. The CC genotype carriers had 78% decreased risk of ADEs compared to those with other genotypes.
This study demonstrates that ADEs induced by ritodrine are associated with ADRB2 gene polymorphisms, as well as the infusion rate of ritodrine in pregnant women with preterm labor.
利托君是一种用于抑制宫缩的β2 肾上腺素能激动剂，尽管存在安全问题，但在欧洲和亚洲已被广泛使用。本研究旨在确定早产患者使用利托君治疗时β2 肾上腺素能受体（ADRB2）基因多态性与药物不良事件（ADEs）之间的关联。
这项随访研究在韩国梨花女子大学木洞医院前瞻性开展。对186例早产孕妇的ADRB2基因的五个单核苷酸多态性（SNP）（rs1042713、rs1042714、rs1042717、rs1042718和rs1042719）进行了分析。rs1042717的AA基因型患者的ADEs发生率显著低于携带G等位基因的患者（p = 0.009）。在多变量分析中，ADEs的预测因素之一是利托君的最大输注速率（调整后比值比4.47，95%置信区间1.31 - 15.25）。rs1042719也是利托君诱发ADEs的一个重要因素。与其他基因型患者相比，CC基因型携带者发生ADEs的风险降低了78%。
本研究表明，早产孕妇使用利托君诱发的ADEs与ADRB2基因多态性以及利托君的输注速率有关。
