RESUMO

Several factors are associated with the progression of chronic hepatitis C: comorbidities, lifestyle, and pathogenic factors, including immune response, apoptosis and heredity. Single nucleotide polymorphisms (SNPs) in the PNPLA3 and TM6SF2 genes are more widely studied genetic risk factors, while CXCL9-11 chemokines produced by hepatocytes in the process of infection are less well studied. Our aim was to evaluate the influence of CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 in liver fibrosis when analysed together with PNPLA3 rs738409 and TM6SF2 rs58542926. The study included 219 patients with chronic hepatitis C. SNP genotyping was performed by real-time PCR. Univariate and multivariate analyses were used to detect the association between SNPs and advanced fibrosis in a recessive genetic model. All SNPs had a minimum allele frequency >5%, and CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 were in high linkage disequilibrium (D' ≥ 0.84). In the multivariate analysis, we observed that male gender (P = 0.000), older age (P = 0.025), moderate to intense inflammatory activity (P = 0.002), moderate to accentuated hepatic steatosis (P = 0.026) and the CT genotype of the TM6SF2 rs58542926 SNP (P = 0.014) presented significant associations with advanced fibrosis. Overall, the CXCL9 rs10336, CXCL10 rs3921, CXCL11 rs4619915 and PNPLA3 rs738409 SNPs did not influence liver fibrosis among patients with chronic hepatitis C.

Assuntos

Quimiocina CXCL10/genética , Quimiocina CXCL11/genética , Quimiocina CXCL9/genética , Hepacivirus , Hepatite C Crônica/genética , Cirrose Hepática/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Quimiocina CXCL10/metabolismo , Quimiocina CXCL11/metabolismo , Quimiocina CXCL9/metabolismo , Feminino , Predisposição Genética para Doença , Genótipo , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Hepatócitos/metabolismo , Humanos , Lipase/genética , Lipase/metabolismo , Cirrose Hepática/virologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade

RESUMO

Host single nucleotide polymorphisms (SNPs) in different genes can play a role in chronic hepatitis C virus (HCV) infection and influence the presence of hepatic fibrosis and comorbidities such as hepatic steatosis. We assessed the combined effect of SNPs in the PNPLA3, MTTP, TM6SF2, and IFNL3/IFNL4 genes in 288 Brazilian patients who were chronically infected with HCV. Hepatic fibrosis was observed in 246 (85.4%) patients and hepatic steatosis in 141 (49.0%) patients. PNPLA3 rs738409 (CG/GG) (P = 0.044) and TM6SF2 rs58542926 (CT) (P = 0.004) were alone associated with fibrosis, and PNPLA3 rs738409 (P < 0.05, in distinct genetic models) was associated with steatosis. Multiple logistic regression of each SNP combined with HCV genotype 3 infection showed that MTTP rs1800591 (GT/TT) combined with HCV genotype 3 was associated with a 6.72-fold increased chance of hepatic steatosis (P = 0.013). In the analysis of SNPs combined 2 by 2, no influence on hepatic fibrosis or steatosis was observed.

Assuntos

Fígado Gorduroso/genética , Hepatite C Crônica/genética , Cirrose Hepática/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Brasil , Proteínas de Transporte/genética , Fígado Gorduroso/virologia , Feminino , Estudos de Associação Genética , Genótipo , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C Crônica/virologia , Humanos , Interferons/genética , Lipase/genética , Cirrose Hepática/virologia , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade