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

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

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.

• Jezik: Angleški jezik
• Ključne besede: inflammation, oxidative stress, polymorphism, hypoxic-ischemic encephalopathy, newborn
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2021
• Št. strani: 11 str.
• Številčenje: Vol. 10, iss. 9, art. 1495
• PID: 20.500.12556/RUL-136339
• UDK: 616-053.2
• ISSN pri članku: 2076-3921
• DOI: 10.3390/antiox10091495
• COBISS.SI-ID: 80001283
• Datum objave v RUL: 25.04.2022

Gradivo je del revije

• Naslov: Antioxidants
• Skrajšan naslov: Antioxidants
• Založnik: MDPI
• ISSN: 2076-3921
• COBISS.SI-ID: 522976025

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 20.09.2021

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: pediatrija, novorojenčki, oksidativni stres, hipoksija, terapevtska podhladitev, epilepsija

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0170
• Naslov: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P3-0343
• Naslov: Etiologija, zgodnje odkrivanje in zdravljenje bolezni pri otrocih in mladostnikih