Genetic polymorphisms, gene–gene interactions and neurologic sequelae at two years follow-up in newborns with hypoxic-ischemic encephalopathy treated with hypothermia

Esih, Katarina (author), Goričar, Katja (author), Soltirovska Šalamon, Aneta (author), Dolžan, Vita (author), Rener-Primec, Zvonka (author)

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 (SOD2 rs4880, CAT rs1001179, GPX1 rs1050450) and inflammatory (NLRP3 rs35829419, CARD8 rs2043211, IL1B rs1143623, IL1B rs16944, IL1B rs10716 76, TNF rs1800629) pathways. Polymorphic CARD8 rs2043211 T allele was less frequent in patients with epilepsy, but the association was not statistically significant. The interaction between CARD8 rs2043211 and IL1B rs16944 was associated with epilepsy after HIE: CARD8 rs2043211 was associated with lower epilepsy risk, but only in carriers of two normal IL1B rs16944 alleles (OR$_{adj}$ = 0.03 95% CI = 0.00–0.55; p$_{adj}$ = 0.019). Additionally, IL1B rs16944 was associated with higher epilepsy risk only in carriers of at least one polymorphic CARD8 rs2043211 (OR$_{adj}$ = 13.33 95% CI = 1.07–166.37; p$_{adj}$ = 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.

• Language: English
• Keywords: inflammation, oxidative stress, polymorphism, hypoxic-ischemic encephalopathy, newborn
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 11 str.
• Numbering: Vol. 10, iss. 9, art. 1495
• PID: 20.500.12556/RUL-136339
• UDC: 616-053.2
• ISSN on article: 2076-3921
• DOI: 10.3390/antiox10091495
• COBISS.SI-ID: 80001283
• Publication date in RUL: 25.04.2022

Record is a part of a journal

• Title: Antioxidants
• Shortened title: Antioxidants
• Publisher: MDPI
• ISSN: 2076-3921
• COBISS.SI-ID: 522976025

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 20.09.2021

Secondary language

• Language: Slovenian
• Keywords: pediatrija, novorojenčki, oksidativni stres, hipoksija, terapevtska podhladitev, epilepsija

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0170
• Name: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0343
• Name: Etiologija, zgodnje odkrivanje in zdravljenje bolezni pri otrocih in mladostnikih