ABSTRACT
Metabolic associated fatty liver disease (MAFLD) is the most prevalent liver disease in Western nations, with high heritability. A recent study of Japanese patients with the disease suggested that TLL1 rs17047200 is associated with fibrosis; whether a similar association is observed in Caucasian patients with MAFLD is unknown. We investigated the association of the TLL1 rs17047200 polymorphism with liver fibrosis in a cohort of Caucasian patients with MAFLD (n = 728). We also investigated whether TLL1 expression is altered during liver injury in humans, in murine models of fibrosis, and in in-vitro. While TLL1 expression is upregulated in the liver of humans with MAFLD and in mice, the rs17047200 variant was not associated with fibrosis or any other histological features, or with hepatic TLL1 expression. In conclusion, the TLL1 rs17047200 variant is not a risk variant for fibrosis in Caucasian patients with MAFLD. However, TLL1 could be involved in the pathogenesis of liver fibrosis.
Subject(s)
Fatty Liver/genetics , Liver Cirrhosis/genetics , Polymorphism, Single Nucleotide , Tolloid-Like Metalloproteinases/genetics , Adult , Animals , Cohort Studies , Fatty Liver/complications , Female , Genetic Variation , Humans , Liver Cirrhosis/complications , Male , Mice , Mice, Inbred C57BL , Middle Aged , Up-RegulationABSTRACT
BACKGROUND AND STUDY AIMS: Host genetic modifiers of the risk and persistence of hepatitis B virus (HBV) infection in the Pakistani population have not been clearly elucidated. Recently, two genome-wide association studies described that STAT4 and IFNL3 variants are associated with different aspects of the course of HBV infection. However, the roles of these variants in the persistence of HBV infection have not been investigated in the HBV-infected population of Pakistan. Therefore, we examined the roles of the STAT4 and IFNL3 variants in a chronic HBV-infected population from the Khyber Pakhtunkhwa (KPK) region of Pakistan. PATIENTS AND METHODS: STAT4 rs7574865 and IFNL3 rs12979860 genotyping were performed in 297 subjects (240 infected with HBV and 57 controls). Statistical analyses were performed using the chi-squared test, Student's t-test, Hardy-Weinberg equilibrium tests and logistic regression models. RESULTS: Among the 297 subjects, compared with the IFNL3 rs12979860 genotype [odds ratio (OR) = 0.7, 95% confidence interval (CI) = 0.39-1.29, p = 0.2), the STAT4 rs7574865 genotype was independently associated with the risk of developing chronic HBV infection [OR = 1.9, 95% CI = 1.09-3.50, p = 0.02]. CONCLUSION: The STAT4 rs7574865 and not the IFNL3 rs12979860 variant is associated with persistence of HBV infection in a Pakistani population from the KPK region.
