Genetic Polymorphisms, Gene–Gene Interactions and Neurologic Sequelae at Two Years Follow-Up in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia
Inflammation and oxidative stress after hypoxic-ischemic brain injury may be modified by genetic variability in addition to therapeutic hypothermia. The aim of our study was to evaluate the association between the polymorphisms in genes of antioxidant and inflammatory pathways in newborns treated wi...
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MDPI AG
2021-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/9/1495 |
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| author | Katarina Esih Katja Goričar Aneta Soltirovska-Šalamon Vita Dolžan Zvonka Rener-Primec |
| author_facet | Katarina Esih Katja Goričar Aneta Soltirovska-Šalamon Vita Dolžan Zvonka Rener-Primec |
| author_sort | Katarina Esih |
| collection | DOAJ |
| description | Inflammation and oxidative stress after hypoxic-ischemic brain injury may be modified by genetic variability in addition to therapeutic hypothermia. The aim of our study was to evaluate the association between the polymorphisms in genes of antioxidant and inflammatory pathways in newborns treated with therapeutic hypothermia and the development of epilepsy or CP at two years follow-up. The DNA of 55 subjects was isolated from buccal swabs. Genotyping using competitive allele-specific PCR was performed for polymorphisms in antioxidant (<i>SOD2</i> rs4880, <i>CAT</i> rs1001179, <i>GPX1</i> rs1050450) and inflammatory (<i>NLRP3</i> rs35829419, <i>CARD8</i> rs2043211, <i>IL1B</i> rs1143623, <i>IL1B</i> rs16944, <i>IL1B</i> rs10716 76, <i>TNF</i> rs1800629) pathways. Polymorphic <i>CARD8</i> rs2043211 T allele was less frequent in patients with epilepsy, but the association was not statistically significant. The interaction between <i>CARD8</i> rs2043211 and <i>IL1B</i> rs16944 was associated with epilepsy after HIE: <i>CARD8</i> rs2043211 was associated with lower epilepsy risk, but only in carriers of two normal <i>IL1B</i> rs16944 alleles (OR<sub>adj</sub> = 0.03 95% CI = 0.00–0.55; p<sub>adj</sub> = 0.019). Additionally, <i>IL1B</i> rs16944 was associated with higher epilepsy risk only in carriers of at least one polymorphic <i>CARD8</i> rs2043211 (OR<sub>adj</sub> = 13.33 95% CI = 1.07–166.37; p<sub>adj</sub> = 0.044). Our results suggest that gene–gene interaction in inflammation pathways might contribute to the severity of brain injury in newborns with HIE treated with therapeutic hypothermia. |
| first_indexed | 2024-03-10T07:55:52Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T07:55:52Z |
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| spelling | doaj.art-2781b26a4f5742cb8835b84de1aaac962023-11-22T11:49:41ZengMDPI AGAntioxidants2076-39212021-09-01109149510.3390/antiox10091495Genetic Polymorphisms, Gene–Gene Interactions and Neurologic Sequelae at Two Years Follow-Up in Newborns with Hypoxic-Ischemic Encephalopathy Treated with HypothermiaKatarina Esih0Katja Goričar1Aneta Soltirovska-Šalamon2Vita Dolžan3Zvonka Rener-Primec4Division of Pediatrics, Department of Child, Adolescent and Developmental Neurology, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaPharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, SloveniaDivision of Pediatrics, Department of Neonatology, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaPharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, SloveniaDivision of Pediatrics, Department of Child, Adolescent and Developmental Neurology, University Medical Centre Ljubljana, 1000 Ljubljana, SloveniaInflammation and oxidative stress after hypoxic-ischemic brain injury may be modified by genetic variability in addition to therapeutic hypothermia. The aim of our study was to evaluate the association between the polymorphisms in genes of antioxidant and inflammatory pathways in newborns treated with therapeutic hypothermia and the development of epilepsy or CP at two years follow-up. The DNA of 55 subjects was isolated from buccal swabs. Genotyping using competitive allele-specific PCR was performed for polymorphisms in antioxidant (<i>SOD2</i> rs4880, <i>CAT</i> rs1001179, <i>GPX1</i> rs1050450) and inflammatory (<i>NLRP3</i> rs35829419, <i>CARD8</i> rs2043211, <i>IL1B</i> rs1143623, <i>IL1B</i> rs16944, <i>IL1B</i> rs10716 76, <i>TNF</i> rs1800629) pathways. Polymorphic <i>CARD8</i> rs2043211 T allele was less frequent in patients with epilepsy, but the association was not statistically significant. The interaction between <i>CARD8</i> rs2043211 and <i>IL1B</i> rs16944 was associated with epilepsy after HIE: <i>CARD8</i> rs2043211 was associated with lower epilepsy risk, but only in carriers of two normal <i>IL1B</i> rs16944 alleles (OR<sub>adj</sub> = 0.03 95% CI = 0.00–0.55; p<sub>adj</sub> = 0.019). Additionally, <i>IL1B</i> rs16944 was associated with higher epilepsy risk only in carriers of at least one polymorphic <i>CARD8</i> rs2043211 (OR<sub>adj</sub> = 13.33 95% CI = 1.07–166.37; p<sub>adj</sub> = 0.044). Our results suggest that gene–gene interaction in inflammation pathways might contribute to the severity of brain injury in newborns with HIE treated with therapeutic hypothermia.https://www.mdpi.com/2076-3921/10/9/1495inflammationoxidative stresspolymorphismhypoxic-ischemic encephalopathynewborn |
| spellingShingle | Katarina Esih Katja Goričar Aneta Soltirovska-Šalamon Vita Dolžan Zvonka Rener-Primec Genetic Polymorphisms, Gene–Gene Interactions and Neurologic Sequelae at Two Years Follow-Up in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia Antioxidants inflammation oxidative stress polymorphism hypoxic-ischemic encephalopathy newborn |
| title | Genetic Polymorphisms, Gene–Gene Interactions and Neurologic Sequelae at Two Years Follow-Up in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia |
| title_full | Genetic Polymorphisms, Gene–Gene Interactions and Neurologic Sequelae at Two Years Follow-Up in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia |
| title_fullStr | Genetic Polymorphisms, Gene–Gene Interactions and Neurologic Sequelae at Two Years Follow-Up in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia |
| title_full_unstemmed | Genetic Polymorphisms, Gene–Gene Interactions and Neurologic Sequelae at Two Years Follow-Up in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia |
| title_short | Genetic Polymorphisms, Gene–Gene Interactions and Neurologic Sequelae at Two Years Follow-Up in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia |
| title_sort | genetic polymorphisms gene gene interactions and neurologic sequelae at two years follow up in newborns with hypoxic ischemic encephalopathy treated with hypothermia |
| topic | inflammation oxidative stress polymorphism hypoxic-ischemic encephalopathy newborn |
| url | https://www.mdpi.com/2076-3921/10/9/1495 |
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