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Influence of cytokine and cytokine receptor gene polymorphisms on the degree of liver damage in patients with chronic hepatitis C.

ABSTRACT: Hepatic fibrosis may be the result of repetitive injury to hepatocytes caused by HCV infection and the immune response to it. Cytokines regulate the inflammatory response to injury and modulate hepatic fibrogenesis. Single nucleotide polymorphisms (SNPs) located in cytokine genes may influence the cytokine expression and secretion that may contribute to hepatic fibrogenesis in HCV infection. The aim of this study was to determine the genotype of 22 SNPs found in the genes of 13 cytokines/cytokine receptors to assess the influence of polymorphic variants on the stage of liver damage in Brazilian patients chronically infected with HCV genotype 1 only. 141 unrelated patients were grouped according to their stage of fibrosis: absence of fibrosis or patients in the initial stages of fibrosis (F0-F2, n = 84), patients with advanced stages of fibrosis or cirrhosis (F3-F4, n = 57), without cirrhosis (F0-F3, n = 103), and with cirrhosis (F4, n = 38). The comparison of frequencies in each sub-sample was performed by 2 × 2 contingency tables using the chi-square or Fisher's exact test. Stepwise logistic regression was also used to assess independent associations between cirrhosis or fibrosis with polymorphic variants. The TNFA-308G:A genotype conferred increased risk of fibrosis and cirrhosis. The TNFA-238G:G genotype was associated with protection from cirrhosis. The IL10-819C:T genotype conferred protection from fibrosis and the IL1B-511C:T genotype conferred increased risk of cirrhosis. Some of these genotypes showed results on the borderline of statistical significance in the bivariate analysis. We conclude that gene variants of cytokines/receptors may influence liver damage in patients chronically infected by HCV genotype 1.

SUBMITTER: Moreira ST

PROVIDER: S-EPMC4864212 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Influence of cytokine and cytokine receptor gene polymorphisms on the degree of liver damage in patients with chronic hepatitis C.

Moreira Sara Tatiana ST Silva Giovanni Faria GF de Moraes Camila Fernanda Verdichio CF Grotto Rejane Maria Tomasini RM de Moura Campos Pardini Maria Inês MI Bicalho Maria da Graça Mda G Moliterno Ricardo Alberto RA

Meta gene 20160421

Hepatic fibrosis may be the result of repetitive injury to hepatocytes caused by HCV infection and the immune response to it. Cytokines regulate the inflammatory response to injury and modulate hepatic fibrogenesis. Single nucleotide polymorphisms (SNPs) located in cytokine genes may influence the cytokine expression and secretion that may contribute to hepatic fibrogenesis in HCV infection. The aim of this study was to determine the genotype of 22 SNPs found in the genes of 13 cytokines/cytokin ...[more]

PMID: 27200267

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Project description:Objective: To investigate the associations of Fc receptor-like 5 (FCRL5) gene polymorphisms and mRNA expression with liver fibrosis in chronic hepatitis B (CHB). Methods: A total of 114 CHB patients with liver fibrosis and 120 CHB patients without liver fibrosis were selected for this study. The gender, age, body mass index (BMI), alanine transaminase (ALT) value, aspartate aminotransferase (AST) value, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) were recorded. Two polymorphisms of the FCRL5 gene (rs6427384 and rs6692977) were genotyped. The mRNA expression level of FCRL5 in peripheral blood monocytes was determined. Results: ALT, AST, APRI, and FIB-4 in patients with fibrosis were significantly higher than those in non-fibrosis patients. There was statistically significant difference between fibrosis and non-fibrosis groups in the genotype distribution (χ2 = 7.805, p = 0.020) and allele frequencies (χ2 = 13.252, p < 0.001) at FCRL5 rs6692977. When compared with CC genotype, the genotype CT or TT at rs6692977 was significantly associated with a increased risk of liver fibrosis in CHB patients (CT vs. CC: OR = 1.921, 95% CI = 1.093-3.375, p = 0.023; TT vs. CC: OR = 2.598, 95% CI = 1.067-6.324, p = 0.031). The mRNA relative expression levels of FCRL5 in patients with liver fibrosis were significantly higher than those in the non-fibrosis group (t = 13.456, p < 0.001). The fibrosis patients carried TT or CT genotype of rs6692977 had significantly higher FCRL5 mRNA expression levels than those carried CC genotype (t = 2.859, p = 0.005). The mRNA expression levels of FCRL5, APRI, and FIB-4 index showed predictive efficacy in liver fibrosis with cut-off values of 0.75 (AUC = 0.896, 95% CI = 0.856-0.935), 0.45 (AUC = 0.852, 95% CI = 0.802-0.902) and 1.84 (AUC = 0.765, 95% CI = 0.703-0.826), respectively. Conclusion: FCRL5 gene rs6692977 polymorphisms and mRNA expression levels are associated with liver fibrosis in CHB patients.

Dataset Information

Influence of cytokine and cytokine receptor gene polymorphisms on the degree of liver damage in patients with chronic hepatitis C.

Publications

Influence of cytokine and cytokine receptor gene polymorphisms on the degree of liver damage in patients with chronic hepatitis C.

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