The rs738409 polymorphism of the PNPLA3 gene is associated with hepatic steatosis and fibrosis in Brazilian patients with chronic hepatitis C

Abstract

BackgroundProspective studies have shown that 80% of acute hepatitis C virus (HCV) cases progress to chronic infection; approximately 10-20% of patients with these conditions will develop liver cirrhosis within 2 to 3 decades, and 1-5% will develop liver cancer. Some studies have indicated that the rs738409 polymorphism of the PNPLA3 gene is associated with steatosis and the progression of advanced fibrosis. This study assessed the contribution of the PNPLA3 rs738409 polymorphism with regard to the steatosis and degree of liver fibrosis in Brazilian patients diagnosed with chronic hepatitis C.MethodsA total of 290 patients were evaluated at the Clinics Hospital of the School of Medicine, University of São Paulo, between 2010 and 2015. The inclusion criteria were age ≥ 18 years and positive anti-HCV antibody and HCV RNA tests. The participants were evaluated based on medical consultation, blood tests, and liver biopsies conducted before specific antiviral therapies were applied. The associations between the rs738409 PNPLA3 gene polymorphism and steatosis and advanced fibrosis were tested under a recessive inheritance model using logistic regression analysis, including age, gender, BMI, ethnicity/color, HOMA-IR, alcohol intake, HCV genotype 3, and the rs58542926 TM6SF2 gene polymorphism as covariates.ResultsThe mean age of the patients was 54.9 years old (range, 28 to 82 years), and 124 (42.8%) patients were male; 226 (77.9%) were white, 43 (14.8%) were pardo, and 21 (7.2%) were black Brazilians. Of the patients included in this study, 133 (45.9%) presented with the CC genotype, 63 (21.7%) with the CG genotype, and 94 (32.4%) with the GG genotype of the PNPLA3 gene I148M variant. We observed that the associations between PNPLA3 rs738409 GG genotype and steatosis was significant (OR: 2.16; 95% CI 1.26-3.72). The same genotype was associated to advanced fibrosis too (OR:2.64; 95% CI 1.26-5.53).ConclusionsAssociations between the rs738409 polymorphism of the PNPLA3 gene genotype GG and hepatic steatosis and advanced fibrosis were observed. Studies are still needed to clarify the influence of these polymorphisms on hepatic steatosis and degree of fibrosis among individuals diagnosed with chronic hepatitis C.Electronic supplementary materialThe online version of this article (10.1186/s12879-017-2887-6) contains supplementary material, which is available to authorized users.

PNPLA3 rs738409 G allele carriers with genotype 1b HCV cirrhosis have lower viral load but develop liver failure at younger age

“…We assume that in these subjects, lipid accumulation in hepatocytes with subsequent steatohepatitis accelerates progression of liver fibrosis caused by the underlying liver disease which is chronic HCV infection. Indeed, coincidence of chronic HCV infection with lipid accumulation and steatohepatitis results in more rapid development of CLF in comparison with HCV-infected individuals without steatohepatitis [12–16]. The hypothesis of two independent synergic processes leading to CLF (HCV infection and steatohepatitis) is further supported by Jimenez-Sousa et al [15] who demonstrated a dose dependent effect of PNPLA3 G allele on the progression of liver stiffness in HCV infected individuals.…”

“…More than fifty studies demonstrating that the PNPLA3 rs738409 G allele is a risk factor for non-alcoholic steatohepatitis (NASH), liver cirrhosis in NASH or alcoholic liver disease have been published in the past decade [5–11]. The same allele was also identified as a risk factor for liver fibrosis and cirrhosis in HCV-monoinfected individuals [12–16] and in those with HCV/HIV coinfection [17–20] and it also turned out to be a predisposing factor of hepatocellular carcinoma (HCC) [21–24]. In a recent study, the increased risk of HCC and PNPLA3 G allele was found only in alcoholic liver disease, but not in non-alcoholic fatty liver disease or viral hepatitis B and C [25].…”

Association between TM6SF2 rs58542926 T/C gene polymorphism and significant liver fibrosis: A meta-analysis

“…Kruk et al [11] C.Manchiero et al [12] U.Vespasiani-Gentilucci et al [13] V.Basyte-Bacev ice et al [14] R.Margherita…”

The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis C

“…Despite the growing investigational experience with TM6SF2 and PNPLA3 polymorphisms in NAFLD, their role in the spectrum of liver disease by the hepatitis C virus is not yet fully defined. Also, there is little data in mixed populations, such as among Brazilians [ 28 ]. In this context, the aim of this study is to describe the prevalence of TM6SF2 and PNPLA3 polymorphisms in Brazilian patients with chronic hepatitis C naïve for antiviral therapy, and to evaluate their association with liver fibrosis, steatosis, and other components of the metabolic syndrome.…”