Genome-wide association study identifies ABCG1 as a susceptibility locus for tick-borne encephalitis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F25%3AN0000148" target="_blank" >RIV/00027162:_____/25:N0000148 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.cell.com/iscience/fulltext/S2589-0042(25)02278-3" target="_blank" >https://www.cell.com/iscience/fulltext/S2589-0042(25)02278-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.isci.2025.114017" target="_blank" >10.1016/j.isci.2025.114017</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Genome-wide association study identifies ABCG1 as a susceptibility locus for tick-borne encephalitis

Popis výsledku v původním jazyce

Tick-borne encephalitis (TBE) is a viral infection of the central nervous system, caused by the tick-borne encephalitis virus (TBEV) presenting clinically as meningitis, meningoencephalitis, and meningoencephalomyelitis. To investigate genetic susceptibility to TBE, and its severe forms, we conducted a genome-wide association study in the European population comprising 1,600 TBE cases and 9,699 controls. We identified several suggestive (p < 1 × 10−5) intronic and exonic variants in ABCG1, the only gene significantly associated with TBE susceptibility. These variants were shown to influence ABCG1 expression in peripheral blood, a finding corroborated by RNA expression analysis. In vitro inhibition or silencing of ABCG1 significantly reduced TBEV replication in both neuronal cells and macrophages, highlighting the potential role of ABCG1 in TBEV biology. Additionally, we detected a genome-wide significant variant within TEX41, located downstream of ZEB1, associated with severe forms of TBE. These findings provide novel insights into the genetic factors underlying TBE susceptibility and severity.

Název v anglickém jazyce

Genome-wide association study identifies ABCG1 as a susceptibility locus for tick-borne encephalitis

Popis výsledku anglicky

Tick-borne encephalitis (TBE) is a viral infection of the central nervous system, caused by the tick-borne encephalitis virus (TBEV) presenting clinically as meningitis, meningoencephalitis, and meningoencephalomyelitis. To investigate genetic susceptibility to TBE, and its severe forms, we conducted a genome-wide association study in the European population comprising 1,600 TBE cases and 9,699 controls. We identified several suggestive (p < 1 × 10−5) intronic and exonic variants in ABCG1, the only gene significantly associated with TBE susceptibility. These variants were shown to influence ABCG1 expression in peripheral blood, a finding corroborated by RNA expression analysis. In vitro inhibition or silencing of ABCG1 significantly reduced TBEV replication in both neuronal cells and macrophages, highlighting the potential role of ABCG1 in TBEV biology. Additionally, we detected a genome-wide significant variant within TEX41, located downstream of ZEB1, associated with severe forms of TBE. These findings provide novel insights into the genetic factors underlying TBE susceptibility and severity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10607 - Virology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

iScience

ISSN

—

e-ISSN

2589-0042

Svazek periodika

28

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

—

Kód UT WoS článku

001629527200001

EID výsledku v databázi Scopus

2-s2.0-105022465615