{"title":"产前依非韦伦的暴露与母体而非胎儿的 CYP2B6 基因型独立相关。","authors":"Oluwasegun Eniayewu, Abdulafeez Akinloye, Babajide Shenkoya, Uche Azuka, Oluseye Bolaji, Ebunoluwa Adejuyigbe, Andrew Owen, Adeniyi Olagunju","doi":"10.1097/FPC.0000000000000542","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Understanding the influence of fetal and maternal genetics on prenatal drug exposure could potentially improve benefit-risk evaluation. In this study, we investigated the impact of two functional polymorphisms in CYP2B6 on prenatal exposure to efavirenz.</p><p><strong>Methods: </strong>Dried blood spot (DBS) samples were collected from HIV-positive pregnant women ( n = 112) and their newborns ( n = 107) at delivery. They were genotyped for single nucleotide polymorphisms in CYP2B6. Efavirenz was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS).</p><p><strong>Results: </strong>Significant correlations were observed in efavirenz concentration between maternal and newborn ( r = 0.46, R2 = 0.21, P < 0.001), and maternal and cord ( r = 0.83, R2 = 0.68, P < 0.001) samples. Median (interquartile range) newborn plasma-to-maternal plasma and cord-to-maternal plasma ratios were 0.85 (0.03-3.49) and 0.78 (0.23-1.96), respectively. Newborn efavirenz concentration in DBS varied significantly based on composite maternal CYP2B6 genotype: fast ( CYP2B6 516GG and 983TT, n = 26), 747 ng/ml (602-1060); intermediate ( CYP2B6 516GT or 983TC n = 50), 1177 ng/ml (898-1765); and slow ( CYP2B6 516GT and 983TC or 516TT or 983CC, n = 14), 3094 ng/ml (2126-3812). Composite newborn CYP2B6 genotype was, however, not significantly associated with prenatal exposure. Efavirenz concentration in newborn stratified as fast ( n = 25), intermediate ( n = 36), and slow metabolizers ( n = 19) from prenatal exposure was 999.7 (774-1285), 1240 (709-1984), and 1792 ng/ml (1201-3188), respectively.</p><p><strong>Conclusion: </strong>The clinical relevance of the observed influence of maternal genetics on prenatal efavirenz exposure requires further investigation.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616417/pdf/","citationCount":"0","resultStr":"{\"title\":\"Prenatal efavirenz exposure is independently associated with maternal, but not fetal CYP2B6 genotype.\",\"authors\":\"Oluwasegun Eniayewu, Abdulafeez Akinloye, Babajide Shenkoya, Uche Azuka, Oluseye Bolaji, Ebunoluwa Adejuyigbe, Andrew Owen, Adeniyi Olagunju\",\"doi\":\"10.1097/FPC.0000000000000542\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Understanding the influence of fetal and maternal genetics on prenatal drug exposure could potentially improve benefit-risk evaluation. In this study, we investigated the impact of two functional polymorphisms in CYP2B6 on prenatal exposure to efavirenz.</p><p><strong>Methods: </strong>Dried blood spot (DBS) samples were collected from HIV-positive pregnant women ( n = 112) and their newborns ( n = 107) at delivery. They were genotyped for single nucleotide polymorphisms in CYP2B6. Efavirenz was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS).</p><p><strong>Results: </strong>Significant correlations were observed in efavirenz concentration between maternal and newborn ( r = 0.46, R2 = 0.21, P < 0.001), and maternal and cord ( r = 0.83, R2 = 0.68, P < 0.001) samples. Median (interquartile range) newborn plasma-to-maternal plasma and cord-to-maternal plasma ratios were 0.85 (0.03-3.49) and 0.78 (0.23-1.96), respectively. Newborn efavirenz concentration in DBS varied significantly based on composite maternal CYP2B6 genotype: fast ( CYP2B6 516GG and 983TT, n = 26), 747 ng/ml (602-1060); intermediate ( CYP2B6 516GT or 983TC n = 50), 1177 ng/ml (898-1765); and slow ( CYP2B6 516GT and 983TC or 516TT or 983CC, n = 14), 3094 ng/ml (2126-3812). Composite newborn CYP2B6 genotype was, however, not significantly associated with prenatal exposure. Efavirenz concentration in newborn stratified as fast ( n = 25), intermediate ( n = 36), and slow metabolizers ( n = 19) from prenatal exposure was 999.7 (774-1285), 1240 (709-1984), and 1792 ng/ml (1201-3188), respectively.</p><p><strong>Conclusion: </strong>The clinical relevance of the observed influence of maternal genetics on prenatal efavirenz exposure requires further investigation.</p>\",\"PeriodicalId\":1,\"journal\":{\"name\":\"Accounts of Chemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616417/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accounts of Chemical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/FPC.0000000000000542\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/FPC.0000000000000542","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/24 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Prenatal efavirenz exposure is independently associated with maternal, but not fetal CYP2B6 genotype.
Objectives: Understanding the influence of fetal and maternal genetics on prenatal drug exposure could potentially improve benefit-risk evaluation. In this study, we investigated the impact of two functional polymorphisms in CYP2B6 on prenatal exposure to efavirenz.
Methods: Dried blood spot (DBS) samples were collected from HIV-positive pregnant women ( n = 112) and their newborns ( n = 107) at delivery. They were genotyped for single nucleotide polymorphisms in CYP2B6. Efavirenz was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Results: Significant correlations were observed in efavirenz concentration between maternal and newborn ( r = 0.46, R2 = 0.21, P < 0.001), and maternal and cord ( r = 0.83, R2 = 0.68, P < 0.001) samples. Median (interquartile range) newborn plasma-to-maternal plasma and cord-to-maternal plasma ratios were 0.85 (0.03-3.49) and 0.78 (0.23-1.96), respectively. Newborn efavirenz concentration in DBS varied significantly based on composite maternal CYP2B6 genotype: fast ( CYP2B6 516GG and 983TT, n = 26), 747 ng/ml (602-1060); intermediate ( CYP2B6 516GT or 983TC n = 50), 1177 ng/ml (898-1765); and slow ( CYP2B6 516GT and 983TC or 516TT or 983CC, n = 14), 3094 ng/ml (2126-3812). Composite newborn CYP2B6 genotype was, however, not significantly associated with prenatal exposure. Efavirenz concentration in newborn stratified as fast ( n = 25), intermediate ( n = 36), and slow metabolizers ( n = 19) from prenatal exposure was 999.7 (774-1285), 1240 (709-1984), and 1792 ng/ml (1201-3188), respectively.
Conclusion: The clinical relevance of the observed influence of maternal genetics on prenatal efavirenz exposure requires further investigation.
期刊介绍:
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.