{"title":"CYP2C9*3增加胎龄大于30周的显著动脉导管未闭婴儿对布洛芬的反应","authors":"Xiang Chen, Yuxi Chen, Tiantian Xiao, Xinran Dong, Yulan Lu, Yanyan Qian, Huijun Wang, Wenhao Zhou","doi":"10.1007/s43657-021-00028-9","DOIUrl":null,"url":null,"abstract":"<p><p>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 CYP2C9*3 and one with CYP2C9*2 were detected. In the GA group of more than 30 GA weeks (GA > 30 wks group), we found higher allele frequency of CYP2C9*3 in Responder group than in Non-responder group (16% vs. 0, <i>p</i> = 0.0391). In the GA group of less than 30 GA weeks (GA ≤ 30 wks group), the sum allele frequency of CYP2C9*3 and CYP2C9*2 had no stastical difference between two groups (Responder group vs. Non-responder group, 13% vs. 11%, <i>p</i> = 0.768). Therefore, we came to conclude that genetic tests of CYP2C9*3 site may benefit the prediction of ibuprofen treatment outcome for hsPDA patients with gestational age of more than 30 weeks.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-021-00028-9.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"2 1","pages":"72-77"},"PeriodicalIF":3.7000,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9590483/pdf/43657_2021_Article_28.pdf","citationCount":"0","resultStr":"{\"title\":\"CYP2C9*3 Increases the Ibuprofen Response of Hemodynamically Significant Patent Ductus Arteriosus in the Infants with Gestational Age of More Than 30 Weeks.\",\"authors\":\"Xiang Chen, Yuxi Chen, Tiantian Xiao, Xinran Dong, Yulan Lu, Yanyan Qian, Huijun Wang, Wenhao Zhou\",\"doi\":\"10.1007/s43657-021-00028-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 CYP2C9*3 and one with CYP2C9*2 were detected. In the GA group of more than 30 GA weeks (GA > 30 wks group), we found higher allele frequency of CYP2C9*3 in Responder group than in Non-responder group (16% vs. 0, <i>p</i> = 0.0391). In the GA group of less than 30 GA weeks (GA ≤ 30 wks group), the sum allele frequency of CYP2C9*3 and CYP2C9*2 had no stastical difference between two groups (Responder group vs. Non-responder group, 13% vs. 11%, <i>p</i> = 0.768). Therefore, we came to conclude that genetic tests of CYP2C9*3 site may benefit the prediction of ibuprofen treatment outcome for hsPDA patients with gestational age of more than 30 weeks.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-021-00028-9.</p>\",\"PeriodicalId\":74435,\"journal\":{\"name\":\"Phenomics (Cham, Switzerland)\",\"volume\":\"2 1\",\"pages\":\"72-77\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2022-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9590483/pdf/43657_2021_Article_28.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Phenomics (Cham, Switzerland)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1007/s43657-021-00028-9\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phenomics (Cham, Switzerland)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s43657-021-00028-9","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
摘要
血流动力学意义显著的动脉导管未闭(hsPDA)是新生儿的一种严重疾病。布洛芬是一种有效的治疗方法，可以减少严重的并发症和手术治疗的需要。一些单核苷酸多态性(snp)与布洛芬代谢、治疗效果和副作用的发生有关。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。这些患者参加了中国新生儿基因组计划(CNGP, ClinicalTrials.gov识别码:NCT03931707)，并获得了下一代测序数据。我们重新分析了测序数据，比较了布洛芬应答组和非布洛芬应答组之间已知的布洛芬相关snp的等位基因频率。共招募了185名胎龄为24 - 40周的hsPDA患者。布洛芬反应组与非反应组在基本资料、布洛芬治疗时间、保守治疗率、并发症、不良反应等方面均无显著差异。共检出携带CYP2C9*3的hsPDA 17例，携带CYP2C9*2的hsPDA 1例。在GA≥30周的GA组(GA > 30周组)中，我们发现应答组CYP2C9*3等位基因频率高于非应答组(16% vs. 0, p = 0.0391)。在GA≤30周的GA组(GA≤30周组)中，CYP2C9*3和CYP2C9*2等位基因频率总和两组间差异无统计学意义(反应组vs非反应组，13% vs 11%， p = 0.768)。因此，我们得出结论，CYP2C9*3位点的基因检测可能有助于预测胎龄大于30周的hsPDA患者布洛芬治疗的结果。补充资料:在线版本包含补充资料，下载地址:10.1007/s43657-021-00028-9。
CYP2C9*3 Increases the Ibuprofen Response of Hemodynamically Significant Patent Ductus Arteriosus in the Infants with Gestational Age of More Than 30 Weeks.
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 CYP2C9*3 and one with CYP2C9*2 were detected. In the GA group of more than 30 GA weeks (GA > 30 wks group), we found higher allele frequency of CYP2C9*3 in Responder group than in Non-responder group (16% vs. 0, p = 0.0391). In the GA group of less than 30 GA weeks (GA ≤ 30 wks group), the sum allele frequency of CYP2C9*3 and CYP2C9*2 had no stastical difference between two groups (Responder group vs. Non-responder group, 13% vs. 11%, p = 0.768). Therefore, we came to conclude that genetic tests of CYP2C9*3 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.
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