CYP2C9*3增加孕龄超过30周婴儿中具有血流动力学意义的动脉导管未闭对布洛芬的反应。
CYP2C9*3 Increases the Ibuprofen Response of Hemodynamically Significant Patent Ductus Arteriosus in the Infants with Gestational Age of More Than 30 Weeks.
作者信息
Chen Xiang, Chen Yuxi, Xiao Tiantian, Dong Xinran, Lu Yulan, Qian Yanyan, Wang Huijun, Zhou Wenhao
机构信息
Departments of Neonatology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, 201102 China.
Shanghai Key Laboratory of Birth Defects, The Translational Medicine Center of Children Development and Disease of Fudan University, Children's Hospital of Fudan University, Shanghai, 201102 China.
出版信息
Phenomics. 2021 Nov 11;2(1):72-77. doi: 10.1007/s43657-021-00028-9. eCollection 2022 Feb.
UNLABELLED
Hemodynamically significant patent ductus arteriosus (hsPDA) is a severe condition in newborns. Ibuprofen is an effective treatment to reduce the severe complications and the need for surgical treatment. Several single-nucleotide polymorphisms (SNPs) were related to the ibuprofen metabolism, treatment effects, and the onset of side effects. The effects of SNPs on hsPDA response after ibuprofen treatment are unknown. Therefore, in this study, we recruited hsPDA patients with standard ibuprofen treatment. Those patients had participated in China Neonatal Genomes Project (CNGP, ClinicalTrials.gov Identifier: NCT03931707) with next-generation sequencing data. We reanalyzed the sequencing data and compared the allele frequencies of known ibuprofen-related SNPs between ibuprofen Responder and Non-responder groups. In total, 185 hsPDA patients were recruited with gestational age (GA) ranging from 24 to 40 weeks. No significant differences were detected in the basic information, period of ibuprofen treatment, rate of conservative treatment, complications, and side effects between ibuprofen Responder group and Non-responder group. Totally, 17 hsPDA carried CYP2C93 and one with CYP2C92 were detected. In the GA group of more than 30 GA weeks (GA > 30 wks group), we found higher allele frequency of CYP2C93 in Responder group than in Non-responder group (16% vs. 0, = 0.0391). In the GA group of less than 30 GA weeks (GA ≤ 30 wks group), the sum allele frequency of CYP2C93 and CYP2C92 had no stastical difference between two groups (Responder group vs. Non-responder group, 13% vs. 11%, = 0.768). Therefore, we came to conclude that genetic tests of CYP2C93 site may benefit the prediction of ibuprofen treatment outcome for hsPDA patients with gestational age of more than 30 weeks.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s43657-021-00028-9.
未标注
血流动力学显著的动脉导管未闭（hsPDA）是新生儿的一种严重病症。布洛芬是一种减少严重并发症和手术治疗需求的有效治疗方法。几种单核苷酸多态性（SNP）与布洛芬代谢、治疗效果及副作用的发生有关。SNP对布洛芬治疗后hsPDA反应的影响尚不清楚。因此，在本研究中，我们招募了接受标准布洛芬治疗的hsPDA患者。这些患者参与了中国新生儿基因组计划（CNGP，ClinicalTrials.gov标识符：NCT03931707）并拥有下一代测序数据。我们重新分析了测序数据，并比较了布洛芬反应者组和无反应者组之间已知的与布洛芬相关SNP的等位基因频率。总共招募了185例hsPDA患者，其胎龄（GA）为24至40周。布洛芬反应者组和无反应者组之间在基本信息、布洛芬治疗时间、保守治疗率、并发症和副作用方面未检测到显著差异。总共检测到17例携带CYP2C93的hsPDA患者和1例携带CYP2C92的患者。在胎龄超过30周的GA组（GA＞30周组）中，我们发现反应者组中CYP2C93的等位基因频率高于无反应者组（16%对0，P = 0.0391）。在胎龄小于30周的GA组（GA≤30周组）中，两组之间CYP2C93和CYP2C92的等位基因频率总和无统计学差异（反应者组对无反应者组，13%对11%，P = 0.768）。因此，我们得出结论，CYP2C93位点的基因检测可能有助于预测胎龄超过30周的hsPDA患者的布洛芬治疗结果。
补充信息
在线版本包含可在10.1007/s43657-021-00028-9获取的补充材料。
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