Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 121 | 2026
Research Articles

Association of p-glycoprotein and bile salt export pump gene polymorphisms with advanced liver disease in hepatitis C virus infected patients

Letícia Bomfim Campos1, Nathália Alves Araújo de Almeida1,2, Marcia Maria Amendola Pires3, Carlos Eduardo Brandão-Mello3, Livia Melo Villar4, José Júnior França de Barros1,+, Vanessa Salete de Paula1

1Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Virologia e Parasitologia Molecular, Rio de Janeiro, RJ, Brasil
2Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Pesquisa Clínica em Neuroinfecções, Rio de Janeiro, RJ, Brasil
3Universidade Federal do Estado do Rio de Janeiro, Hospital Universitário Gaffrée e Guinle, Serviço de Gastroenterologia, Rio de Janeiro, RJ, Brasil
4Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hepatites Virais, Rio de Janeiro, RJ, Brasil

DOI: 10.1590/0074-02760250173
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ABSTRACT

BACKGROUND Single-nucleotide polymorphisms (SNPs) can influence the hepatitis C virus (HCV) infection and progression. ABCB1-gene SNPs - c.1236C>T, c.2677G>T and c.3435C>T - are associated with drug efficacy, hepatotoxicity, and liver injury. ABCB11 c.1331T>C is associated with cholestasis and altered bilirubin levels, potentially worsening liver disease.
OBJECTIVE To investigate the impact of ABCB1 and ABCB11 SNPs on disease progression in chronic HCV patients.
METHODS A total of 232 HCV patients unresponsive to conventional therapy were analysed. Serum samples were genotyped by quantitative polymerase chain reaction (qPCR), and the genotype and allele-based analysis was performed using RStudio.
FINDINGS Cirrhosis was present in 59.1% of patients, along with diabetes (28.4%) and hepatic steatosis (46.1%). The most frequent ABCB1 variant allele was c.3435C>T (36.8%), followed by c.1236C>T (30.8%) and c.2677G>T (26.7%). The ABCB11 c.1331CC genotype was observed in 31.3% of the cohort. Genotypes 1236TT and 2677TT and their alleles were associated with lower total cholesterol. 2677TT genotype and 2677T allele were associated with lower high-density lipoprotein. Patients with 1331CC genotype had higher aspartate aminotransferase levels, and the 1331CC genotype was a risk factor for cirrhosis. A fully variant combined allele (1236T and 2677T and 3435T and 1331C) was associated with higher alpha-fetoprotein and lower cholesterol.
MAIN CONCLUSIONS ABCB1 and ABCB11 SNPs are associated with worse clinical outcomes in HCV, underscoring their relevance in disease monitoring.

key words: hepatitis C ATP-binding cassette ABCB1 ABCB11 drug resistance genetic factors
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Financial support: CAPES [No. 88887.623119/2021-00 (master’s scholarship to Campos LB)], CNPq, FAPERJ.
+ Corresponding author: barros@ioc.fiocruz.br | ORCID https://orcid.org/0000-0002-4288-8680
Received 12 July 2025
Accepted 19 March 2026

HOW TO CITE
Campos LB, de Almeida NAA, Pires MMA, Brandão-Mello CE, Villar LM, de Barros JJF, et al. Association of p-glycoprotein and bile salt export pump gene polymorphisms with advanced liver disease in hepatitis C virus infected patients. Mem Inst Oswaldo Cruz. 2025; 121: e250173.

HANDLING EDITOR
Marcelo Ribeiro-Alves | ORCID https://orcid.org/0000-0002-8663-3364

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