{"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":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"253-260"},"PeriodicalIF":1.7000,"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\":19763,\"journal\":{\"name\":\"Pharmacogenetics and genomics\",\"volume\":\" \",\"pages\":\"253-260\"},\"PeriodicalIF\":1.7000,\"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\":\"Pharmacogenetics and genomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/FPC.0000000000000542\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenetics and genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/FPC.0000000000000542","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/24 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","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:
Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.