Diet-related adaptive gene (DRAG) polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico’s population is comprised of Amerindians (AM) and Mestizos who have variable AM, European (EUR) and African genetic ancestry and an increased risk of nutrition-related chronic diseases. Nutritional advice based on the Mexican genome and the traditional food culture is needed to develop preventive and therapeutic strategies. Therefore, we aimed to provide a prevalence profile of several DRAG polymorphisms in the Mexican population, including Central West (CW) Mexico subpopulations. Geographic heat maps were built using ArcGIS10 (Esri, Redlands, CA, USA) software, based on the published data of the MTHFR C677T (rs1801133), ABCA1 Arg230Cys (rs9282541), APOE T388C (rs429358)/C526T (rs7412), LCT C-13910T (rs4988235) polymorphisms and AMY1 copy number variation (CNV). Also, new data obtained by allelic discrimination-real-time polymerase chain reaction (RT-PCR) assays for the MTHFR, ABCA1, and APOE polymorphisms as well as the AMY1 CNV in the CW Mexico subpopulations with different proportions of AM and EUR ancestry were included. In the CW region, the highest frequency of the MTHFR 677T, ABCA1 230C and APOE ε4 adaptive alleles was observed in the AM groups, followed by Mestizos with intermediate AM ancestry. The LCT-13910T allele frequency was highest in Mestizos-EUR but extremely low in AM, while the AMY1 diploid copy number was 6.82 ± 3.3 copies. Overall, the heat maps showed a heterogeneous distribution of the DRAG polymorphisms, in which the AM groups revealed the highest frequencies of the adaptive alleles followed by Mestizos. Given these genetic differences, genome-based nutritional advice should be tailored in a regionalized and individualized manner according to the available foods and Mexican traditional food culture that may lead to a healthier dietary pattern.

Purpose: This study aimed to analyze the association of the apolipoprotein E (ApoE) polymorphisms with type 2 diabetes mellitus (T2DM) among the admixed population of West Mexico. Patients and Methods: ApoE genotypes were determined in 168 T2DM patients and 449 non-diabetic control subjects from the general admixed population of West Mexico. The non-diabetic subjects were stratified according to body mass index (BMI) in normal weight (n=186), overweight (n=138), and obesity (n=125). ApoE genotypes were assessed by using a TaqMan allelic discrimination assay, insulin resistance (IR) by HOMA-IR, and biochemistry with a dry chemistry assay. Results: The rate of dyslipidemias and IR increased by BMI category among the control subjects. The greater shift in the prevalence of dyslipidemia was observed from normal weight (51.4%) to overweight (76.6%), p< 0.01. Normal weight or obese e4 allele carriers had a higher level of total cholesterol and hypercholesterolemia than non-e4 carriers. Among the T2DM patients, the e2 carriers had abnormal HOMA-IR value than the non-e2 carriers (p=0.002). Comparatively, between the T2DM patients vs non-diabetics, the e2e3 genotype or e2 allele conferred a higher risk for T2DM (adjusted OR= 2.36, 95% CI 1.28– 4.34, p=0.006 and adjusted OR=2.1, 95% Cl 1.20– 3.79, p=0.009, respectively). Conclusion: The ApoE e2 allele was associated with IR and the risk of T2DM in subjects from the general admixed population of West Mexico.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity and other cardiometabolic risk factors. MASLD has rapidly become the most common cause of liver disease worldwide, currently affecting 38% of the global population. Excess weight causes chronic inflammation and the activation of different pathways involved in liver damage. MASLD can progress from simple steatosis to steatohepatitis, giving way to its inflammatory component, metabolic dysfunction-associated steatohepatitis (MASH), previously recognized as non-alcoholic steatosis hepatitis (NASH). Chronic hepatitis C virus (HCV) infection remains a significant challenge to liver health as it triggers hepatic inflammation, metabolic disruption, and hepatic steatosis. The convergence of MASLD and chronic HCV infection can significantly alter the course of liver disease and accelerate the progression to severe liver damage. Currently, HCV treatment has a high cure rate. However, in patients who achieve a sustained virological response after treatment with direct-acting antivirals, weight gain, and excessive calorie intake may contribute to increased liver steatosis and a higher risk of liver disease progression. Therefore, the effective clinical and nutritional management of HCV patients, both before and after viral eradication, is crucial to reducing the risk of death from hepatocellular carcinoma. Understanding the complex interactions between MASLD and HCV infection is crucial for managing these patients appropriately. Herein, host and viral mechanisms inducing liver damage during the coexistence of MASLD and HCV infection are described, and their therapeutic and dietary management are discussed.

Hepatitis C virus (HCV) infection is influenced by genetic (e.g., APOE polymorphisms) and environmental factors between the virus and the host. HCV modulates the host’s lipid metabolism but dietary components influence lipids and in vitro HCV RNA replication. Few data exist on the role of dietary features or patterns (DPs) in HCV infection. Herein, we aimed to evaluate the nutritional profiles of chronic HCV (CHC) and spontaneous clearance (SC) Mexican patients in the context of APOE alleles and their correlation with HCV-related variables. The fibrosis-related APOEε3 allele prevailed in CHC and SC patients, who had four DPs (“meat and soft drinks”, DP1; “processed animal and fried foods”, DP2; “Mexican-healthy”, DP3; and “fish-rich”, DP4). In CHC subjects, polyunsaturated fatty acid intake (PUFA ≥ 4.9%) was negatively associated, and fiber intake (≥21.5 g/day) was positively associated with a high viral load (p < 0.036). High adherence to fish-rich DP4 was associated with a higher frequency of CHC individuals consuming PUFA ≥ 4.9% (p = 0.004) and low viral load (p = 0.036), but a lower frequency of CHC individuals consuming fiber ≥21.5 g/day (p = 0.038). In SC and CHC individuals, modifying unhealthy DPs and targeting HCV-interacting nutrients, respectively, could be part of a nutritional management strategy to prevent further liver damage.

Genetic variation in PNPLA3 influences liver fat accumulation and hepatocellular injury in various liver diseases. However, the role of PNPLA3 intronic polymorphisms in hepatic damage among hepatitis C virus (HCV) patients remains unclear. This study aims to investigate the association of three intronic PNPLA3 polymorphisms (rs4823173, rs2896019, and rs2281135) with liver injury in HCV-infected patients with spontaneous HCV clearance (SC) and chronic hepatitis C (CHC). A total of 218 HCV-positive individuals were classified into SC (n = 64) or CHC (n = 154) groups. PNPLA3 genotypes were determined by qPCR using TaqMan probes and liver damage through serum markers, noninvasive index, and liver stiffness. Among SC patients, the genotypes AA-rs4823173, GG-rs2896019, and AA-rs2281135 were associated with higher AST, ALT, and APRI, as well as decreased platelet counts, compared with patients homozygous for the non-risk genotypes (p < 0.05). No associations were found in CHC patients. The three polymorphisms were in perfect linkage disequilibrium (r² = 1). The risk haplotype AGA was associated with higher AST and ALT, as well as lower platelet counts (p < 0.05) in SC patients. PNPLA3 intronic polymorphisms and their association with serum liver injury markers could help identify hepatic injury in HCV-negative patients.