Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons
Background: Neonatal opioid withdrawal syndrome (NOWS), arises due to increased opioid use during pregnancy. Cytochrome P450 (CYP) enzymes play a pivotal role in metabolizing a wide range of substances in the human body, including opioids, other drugs, toxins, and endogenous compounds. The associati...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-01-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1292148/full |
| _version_ | 1827386133631205376 |
|---|---|
| author | Uppala Radhakrishna Uppala Radhakrishna Senthilkumar Sadhasivam Rupa Radhakrishnan Ariadna Forray Srinivas B. Muvvala Raghu P. Metpally Saumya Patel Rakesh M. Rawal Sangeetha Vishweswaraiah Ray O. Bahado-Singh Swapan K. Nath |
| author_facet | Uppala Radhakrishna Uppala Radhakrishna Senthilkumar Sadhasivam Rupa Radhakrishnan Ariadna Forray Srinivas B. Muvvala Raghu P. Metpally Saumya Patel Rakesh M. Rawal Sangeetha Vishweswaraiah Ray O. Bahado-Singh Swapan K. Nath |
| author_sort | Uppala Radhakrishna |
| collection | DOAJ |
| description | Background: Neonatal opioid withdrawal syndrome (NOWS), arises due to increased opioid use during pregnancy. Cytochrome P450 (CYP) enzymes play a pivotal role in metabolizing a wide range of substances in the human body, including opioids, other drugs, toxins, and endogenous compounds. The association between CYP gene methylation and opioid effects is unexplored and it could offer promising insights.Objective: To investigate the impact of prenatal opioid exposure on disrupted CYPs in infants and their anticipated long-term clinical implications.Study Design: DNA methylation levels of CYP genes were analyzed in a cohort of 96 placental tissues using Illumina Infinium MethylationEPIC (850 k) BeadChips. This involved three groups of placental tissues: 32 from mothers with infants exposed to opioids prenatally requiring pharmacologic treatment for NOWS, 32 from mothers with prenatally opioid-exposed infants not needing NOWS treatment, and 32 from unexposed control mothers.Results: The study identified 20 significantly differentially methylated CpG sites associated with 17 distinct CYP genes, with 14 CpGs showing reduced methylation across 14 genes (CYP19A1, CYP1A2, CYP4V2, CYP1B1, CYP24A1, CYP26B1, CYP26C1, CYP2C18, CYP2C9, CYP2U1, CYP39A1, CYP2R1, CYP4Z1, CYP2D7P1 and), while 8 exhibited hypermethylation (CYP51A1, CYP26B1, CYP2R1, CYP2U1, CYP4X1, CYP1A2, CYP2W1, and CYP4V2). Genes such as CYP1A2, CYP26B1, CYP2R1, CYP2U1, and CYP4V2 exhibited both increased and decreased methylation. These genes are crucial for metabolizing eicosanoids, fatty acids, drugs, and diverse substances.Conclusion: The study identified profound methylation changes in multiple CYP genes in the placental tissues relevant to NOWS. This suggests that disruption of DNA methylation patterns in CYP transcripts might play a role in NOWS and may serve as valuable biomarkers, suggesting a future pathway for personalized treatment. Further research is needed to confirm these findings and explore their potential for diagnosis and treatment. |
| first_indexed | 2024-03-08T15:38:38Z |
| format | Article |
| id | doaj.art-4dbab8a847cb42749fcafff78c1a1426 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-08T15:38:38Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-4dbab8a847cb42749fcafff78c1a14262024-01-09T15:32:08ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-01-011410.3389/fgene.2023.12921481292148Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizonsUppala Radhakrishna0Uppala Radhakrishna1Senthilkumar Sadhasivam2Rupa Radhakrishnan3Ariadna Forray4Srinivas B. Muvvala5Raghu P. Metpally6Saumya Patel7Rakesh M. Rawal8Sangeetha Vishweswaraiah9Ray O. Bahado-Singh10Swapan K. Nath11Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Obstetrics and Gynecology, Corewell Health William Beaumont University Hospital, Royal Oak, MI, United StatesDepartment of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, United StatesDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, United StatesDepartment of Molecular and Functional Genomics, Geisinger, Danville, PA, United StatesDepartment of Botany, Bioinformatics and Climate Change Impacts Management, School of Science, Gujarat University, Ahmedabad, IndiaDepartment of Life Sciences, School of Sciences, Gujarat University, Ahmedabad, IndiaDepartment of Obstetrics and Gynecology, Corewell Health William Beaumont University Hospital, Royal Oak, MI, United StatesDepartment of Obstetrics and Gynecology, Corewell Health William Beaumont University Hospital, Royal Oak, MI, United StatesArthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United StatesBackground: Neonatal opioid withdrawal syndrome (NOWS), arises due to increased opioid use during pregnancy. Cytochrome P450 (CYP) enzymes play a pivotal role in metabolizing a wide range of substances in the human body, including opioids, other drugs, toxins, and endogenous compounds. The association between CYP gene methylation and opioid effects is unexplored and it could offer promising insights.Objective: To investigate the impact of prenatal opioid exposure on disrupted CYPs in infants and their anticipated long-term clinical implications.Study Design: DNA methylation levels of CYP genes were analyzed in a cohort of 96 placental tissues using Illumina Infinium MethylationEPIC (850 k) BeadChips. This involved three groups of placental tissues: 32 from mothers with infants exposed to opioids prenatally requiring pharmacologic treatment for NOWS, 32 from mothers with prenatally opioid-exposed infants not needing NOWS treatment, and 32 from unexposed control mothers.Results: The study identified 20 significantly differentially methylated CpG sites associated with 17 distinct CYP genes, with 14 CpGs showing reduced methylation across 14 genes (CYP19A1, CYP1A2, CYP4V2, CYP1B1, CYP24A1, CYP26B1, CYP26C1, CYP2C18, CYP2C9, CYP2U1, CYP39A1, CYP2R1, CYP4Z1, CYP2D7P1 and), while 8 exhibited hypermethylation (CYP51A1, CYP26B1, CYP2R1, CYP2U1, CYP4X1, CYP1A2, CYP2W1, and CYP4V2). Genes such as CYP1A2, CYP26B1, CYP2R1, CYP2U1, and CYP4V2 exhibited both increased and decreased methylation. These genes are crucial for metabolizing eicosanoids, fatty acids, drugs, and diverse substances.Conclusion: The study identified profound methylation changes in multiple CYP genes in the placental tissues relevant to NOWS. This suggests that disruption of DNA methylation patterns in CYP transcripts might play a role in NOWS and may serve as valuable biomarkers, suggesting a future pathway for personalized treatment. Further research is needed to confirm these findings and explore their potential for diagnosis and treatment.https://www.frontiersin.org/articles/10.3389/fgene.2023.1292148/fullcytochromesbiomarkeropioid useneonatal opioid withdrawal syndrome CYP19A1CYP1A2CYP4V2 |
| spellingShingle | Uppala Radhakrishna Uppala Radhakrishna Senthilkumar Sadhasivam Rupa Radhakrishnan Ariadna Forray Srinivas B. Muvvala Raghu P. Metpally Saumya Patel Rakesh M. Rawal Sangeetha Vishweswaraiah Ray O. Bahado-Singh Swapan K. Nath Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons Frontiers in Genetics cytochromes biomarker opioid use neonatal opioid withdrawal syndrome CYP19A1 CYP1A2 CYP4V2 |
| title | Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons |
| title_full | Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons |
| title_fullStr | Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons |
| title_full_unstemmed | Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons |
| title_short | Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons |
| title_sort | placental cytochrome p450 methylomes in infants exposed to prenatal opioids exploring the effects of neonatal opioid withdrawal syndrome on health horizons |
| topic | cytochromes biomarker opioid use neonatal opioid withdrawal syndrome CYP19A1 CYP1A2 CYP4V2 |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1292148/full |
| work_keys_str_mv | AT uppalaradhakrishna placentalcytochromep450methylomesininfantsexposedtoprenatalopioidsexploringtheeffectsofneonatalopioidwithdrawalsyndromeonhealthhorizons AT uppalaradhakrishna placentalcytochromep450methylomesininfantsexposedtoprenatalopioidsexploringtheeffectsofneonatalopioidwithdrawalsyndromeonhealthhorizons AT senthilkumarsadhasivam placentalcytochromep450methylomesininfantsexposedtoprenatalopioidsexploringtheeffectsofneonatalopioidwithdrawalsyndromeonhealthhorizons AT ruparadhakrishnan placentalcytochromep450methylomesininfantsexposedtoprenatalopioidsexploringtheeffectsofneonatalopioidwithdrawalsyndromeonhealthhorizons AT ariadnaforray placentalcytochromep450methylomesininfantsexposedtoprenatalopioidsexploringtheeffectsofneonatalopioidwithdrawalsyndromeonhealthhorizons AT srinivasbmuvvala placentalcytochromep450methylomesininfantsexposedtoprenatalopioidsexploringtheeffectsofneonatalopioidwithdrawalsyndromeonhealthhorizons AT raghupmetpally placentalcytochromep450methylomesininfantsexposedtoprenatalopioidsexploringtheeffectsofneonatalopioidwithdrawalsyndromeonhealthhorizons AT saumyapatel placentalcytochromep450methylomesininfantsexposedtoprenatalopioidsexploringtheeffectsofneonatalopioidwithdrawalsyndromeonhealthhorizons AT rakeshmrawal placentalcytochromep450methylomesininfantsexposedtoprenatalopioidsexploringtheeffectsofneonatalopioidwithdrawalsyndromeonhealthhorizons AT sangeethavishweswaraiah placentalcytochromep450methylomesininfantsexposedtoprenatalopioidsexploringtheeffectsofneonatalopioidwithdrawalsyndromeonhealthhorizons AT rayobahadosingh placentalcytochromep450methylomesininfantsexposedtoprenatalopioidsexploringtheeffectsofneonatalopioidwithdrawalsyndromeonhealthhorizons AT swapanknath placentalcytochromep450methylomesininfantsexposedtoprenatalopioidsexploringtheeffectsofneonatalopioidwithdrawalsyndromeonhealthhorizons |