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Introduction and Objectives: Hepatocellular carcinoma (HCC) is one of the neoplasms with the highest mortality worldwide. The causes of the development of HCC have been related to hepatitis B virus and exposure to aflatoxin B1; however, chronic alcohol use, nonalcoholic fatty liver disease, and hepatitis C virus infection are the most important risk factors for developing HCC. The establishment of animal models of HCC is crucial for both basic and translational studies of hepatocellular carcinoma and is a valuable tool to identify alterations during the progression of the disease. This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a model of chemical hepatocarcinogenesis by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Materials and Methods: Twelve Wistar rats weighing 180 to 200 g were divided into control and damage groups: rats were treated with DEN (50 mg/kg/wk) i.p and an intragastric dose of 2-AAF (25 mg/kg/wk) for 18 weeks. Serum clinical biochemistry was performed on VITROS Chemistry System 350® equipment. Masson's trichrome and Hematoxylin-Eosin stains were performed on the liver tissue. Relative gene expression was performed by RT-qPCR in LightCycler®96. Results: The damage group had significant increases in total cholesterol, HDL-C, AST, ALT, ALKP, and GGT. Furthermore, histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa distributed between portal triads and collagen fibers through the hepatic sinusoids. The expression of TGFb1 was significantly increased (p

Background. The prevalence of two functional polymorphisms (rs1127354 and rs7270101) of the inosine triphosphatase (ITPA) gene associated with ribavirin-induced hemolytic anemia (RIHA) during antiviral therapy for hepatitis C virus (HCV) infection varies by ethnicity. In Mexico, the distribution of these polymorphisms among Native Amerindians (NA) and admixed population (Mestizos) is unknown. This study aimed to determine the prevalence of the ITPA polymorphisms among healthy NA and Mestizos, as well as in HCV patients from West Mexico.Material and methods. In a cross-sectional study, 600 unrelated subjects (322 Mestizos, 100 NA, and 178 treatment-naïve, HCV-infected Mestizos patients) were enrolled. A medical history was registered. ITPA genotype was determined by Real-Time PCR. Fst-values and genetic relatedness between study and reference populations were assessed.Results. The frequency of the risk genotypes rs1127354CC and rs7270101AA was higher among NA (98-100%) than in Mestizos (87-92.9%), (p < 0.05). The NA presented the highest prevalence of the rs1127354CC genotype reported worldwide. The Fst-values revealed a genetic relatedness among Mexican NA, South Americans and African populations (p > 0.05). The frequency of the predicted risk for RIHA was higher among NA (98%) than in Mestizos (80.5%) and HCV-infected patients (81.5%) (p < 0 .01). The CC/AA alleles were associated with lower values of total bilirubin, aspartate/alanine aminotransferases, and aspartate-to-plate-let-ratio-index score among HCV-patients.Conclusion. A high prevalence of the ITPA polymorphisms associated with RIHA was found in Mexican NA. These polymorphisms could be a useful tool for evaluating potential adverse effects and the risk or benefit of antiviral therapy in Mexicans and other admixed populations.

Background. Alcohol intake has been associated with the bitter taste receptor T2R38. TAS2R38 gene expresses two common haplotypes: PAV and AVI. It has been reported that AVI homozygotes consume more alcohol than heterozygotes and PAV homozygotes. The aim of this study was to determine the prevalence of the TAS2R38 haplotypes among Mexican-Mestizo population and to analyze its association with alcohol intake.Material and methods. In a cross-sectional study, a total of 375 unrelated Mestizo individuals were genotyped for TAS2R38 polymorphisms (A49P, V262A and I296V) by a Real-Time PCR System (TaqMan). Haplotype frequencies were calculated. Association of TAS2R38 haplotypes with alcohol intake was estimated in drinkers (DRS) and nondrinkers (NDRS).Results. Two haplotypes accounted for over 96% of all haplotypes (AVV, 60%, and PAI, 36.5%). The frequency of AVV homozygotes was significantly higher in DRS than NDRS (47.2 vs. 32.2%, respectively; p < 0.05). Additionally, the AVV/AVV genotype was associated with alcohol intake when compared with heterozygotes and PAI homozygotes (OR = 1.79, 95% CI 1.13-2.84, p < 0.05 and OR = 2.23, 95% CI 1.11-4.48; p < 0.05, respectively).Conclusions. In conclusion, two TAS2R38 haplotypes (AVV and PAI) prevailed in Mexican-Mestizo population. The novel AVV haplotype was associated with alcohol intake. The high prevalence of this allelic profile in our population could help to explain, at least in part, the preference for alcohol among the Mexicans.

Background. Gallstone disease (GSD) is a common chronic disease in the Western hemisphere, yet environmental and genetic factors may be responsible for the variations in the prevalence of GSD among populations.Aim. To analyze the relationship of the ApoE and FABP2 polymorphisms with diet, physical activity and emotional health in patients with GSD from West Mexico.Material and methods. A total of 120 patients with GSD and 370 healthy subjects were enrolled. Anthropometric, biochemical, nutritional, clinical and physical activity parameters were measured. ApoE and FABP2 genotypes were assesed by PCR-RFLPs assays.Results: ApoE E3/E4 genotype and the ApoE E4 allele was highly prevalent among the GSD patients compared to the controls (32% vs. 12.0% and 22% vs. 8.4% respectively p < 0.01). Patients with the Apo E4 allele showed an upward trend of cholesterol levels compared to non-Apo E4 allele carriers (E4 186 ± 30 mg/dL; E3 143 ± 37 mg/dL; E2 129 ± 34 mg/dL). High triglyceride levels were associated with patients that were FABP2 Thr54 allele carriers (p < 0.05) but lacked association with GSD. This may be due to changes in dietary fats after GSD diagnosis, masking the clinical course of the disease. Sedentary lifestyle and negative emotions were detected in 83% and 63% of patients, respectively.Conclusion. These data suggest that the Apo E4 allele could confer genetic susceptibility for the development of GSD among the Mexican population. The Ala54Thr polymorphism of FABP2 was associated with high triglycerides levels, but not to GSD; suggesting that environmental factors modulate such susceptibility.

Gallstone disease (GSD) is the result of the interaction between genetic and environmental factors and it is a major disease cause of surgery with high costs to health systems. Worldwide prevalence varies according to the ethnic population suggesting that high prevalence of GSD in certain ethnic groups is due to the presence of genetic factors implicated in different metabolic pathways. However, environmental factors play a determinant role in gene expression. This review summarizes the genes involved in biliary salt and cholesterol synthesis, lipids transport and the Lith genes. Future studies should be focused on the study of interactions between genetic and environmental factors which could be specific for each population.