Hepatitis C virus-infected patients carriers of the TT (C*52T, rs14158) genotype of the LDL receptor and Apo3 present severe liver damage in West Mexico

Abstract

Introduction and Objectives: The clinical course of hepatitis C virus infection (HCV) is modulated by environmental factors and genetic polymorphisms that interact with the virus, such as the low-density lipoprotein receptor (LDLR) and ligand Apolipoprotein E (ApoE); both are associated with lipid metabolism. However, the relationship of these genes with liver damage has not been jointly evaluated in Mexicans. The study aimed to identify a relationship between the LDLR polymorphism (C*52T, rs14158) and ApoE haplotype in anti-HCV positive patients with liver damage in a subpopulation of West Mexico. Materials and Patients: This cross-sectional study included 152 naïve anti-HCV positive patients; 110 were viral load (VL) positive (+ve), and 42 were VL negative(-ve). A medical-nutritional evaluation was registered. LDLR and ApoE genotypes were assessed by allelic discrimination. Comparative statistical analysis was performed between VL+ve and VL-ve adjusted by genotype distribution and liver damage. Written informed consent was obtained from the participants. The Institutional Review Board approved this study. Results: The patients (85F/67M) were 49.8±12 years of age with a BMI of 27.7±5.4. VL +ve patients showed glucose homeostasis abnormalities (glucose >100 mg/dL, HOMA-IR >2.5); low levels of cholesterol, triglycerides, VLDL, and LDL, compared to VL-ve patients (p<0.001), as well as high-above-normal ALT, AST, GGT (p<0.001) and low platelets (p<0.001). A 61.1% (58/95) of the VL+ve patients had a high risk for fibrosis (FIB-4), and 35.7% (35/98) had severe fibrosis (APRI). A 10% (11/110) of the VL+ve patients were carriers of the TT LDLR/ApoE3 genotype in which 90% (10/11) had moderate/severe liver damage compared to the C allele carriers (CC, CT), whereas the VL-ve patients had 0% of the TT LDLR genotype (p=0.035) with a lower proportion of liver damage. Conclusions: The presence of the TT LDLR/ApoE3 genotypes in VL+ve patients with hepatic function abnormalities suggests that it may be a valuable marker for risk of liver damage to avoid disease progression and to implement preventive strategies among the Mexican population.