Antibodies Reactive to Leptin in Adults with Type 2 Diabetes and Its Relationship with Clinical, Metabolic and Cardiovascular Risk Parameters.

BACKGROUND AND AIMS: Patients with obesity and type 2 diabetes (T2D) have shown alterations in the affinity of IgG anti-leptin antibodies which are possibly related to metabolic alterations. In the present exploratory study, we analyzed serum samples from adults with T2D classified by body mass index (BMI) and evaluated the relationship of IgG anti-leptin antibodies with body composition, metabolic and cardiovascular risk parameters. METHODS: Serum IgG anti-leptin antibodies (total, free and immune complexes fractions) were measured by in-house ELISA. Body composition, metabolic biomarkers (glucose, glycated hemoglobin, lipid profile, insulin, leptin) and cardiometabolic risk indexes (AIP, HOMA-IR, HOMA-ß) were evaluated in one hundred T2D patients. RESULTS: Patients with T2D and obesity presented a decrease in the percentage of IgG anti-leptin immune complexes compared to patients with T2D and overweight (p < 0.0053). Negative correlations of IgG anti-leptin immune complexes with triglycerides (TG) (r=-0.412, p = 0.023) and VLDL-C (r=-0.611, p = 0.017) were found in normal weight T2D patients. Free IgG anti-leptin antibodies correlated positively with TC (r = 0.390, p = 0.032) and LDL-C (r = 0.458, p = 0.011) in overweight individuals with T2D. Finally, total IgG anti-leptin antibodies correlated positively with leptin hormone levels (r = 0.409, p = 0.024) and negatively with HOMA-IR (r =-0.459, p = 0.012) in T2D patients with obesity. CONCLUSIONS: The decrease of IgG anti-leptin immune complexes observed in patients with T2D and obesity suggests a reduction in antibody affinity to the hormone that may impact its transport and signaling, lipid, lipoprotein and insulin metabolism.

SARS-CoV-2 and Dengue Virus Coinfection in a Mexican Pediatric Patient: A Case Report from Early Molecular Diagnosis.

Mexico is an endemic region for dengue virus (DENV). The increase in this disease coincides with outbreaks of COVID-19, both of which are single-stranded positive RNA viruses. These characteristics make it difficult to distinguish each disease because they share clinical and laboratory features, which can consequently result in misdiagnoses. This is why the use of precision confirmatory tests (qRT-PCR) are crucial for early diagnosis. We herein report a pediatric patient who presented a coinfection for DENV and COVID-19, "SARS-CoV-2/Dengue". This patient initially presented a fever, cough, and headache and, three days later, developed generalized pain and epistaxis. Blood studies revealed thrombocytopenia and leukopenia, and the patient was admitted to the hospital for a probable DENV infection. Within 48 h, qRT-PCR tests specific for SARS-CoV-2 and DENV were performed and resulted as positive. The patient immediately received pharmacological treatment with azithromycin, oseltamivir, and metamizole. During hospitalization (9 days), the patient had no signs of respiratory distress and maintained normal body temperature and normal blood oxygen saturation. This case warns of the need for early diagnosis and adequate clinical and pharmacological management in the face of a "SARS-CoV-2/Dengue" coinfection. Early molecular detection of both viruses and timely treatment helped the patient to achieve a favorable recovery.

Effect of Metformin on Glycemic Control Regarding Carriers of the SLC22A1/OCT1 (rs628031) Polymorphism and Its Interactions with Dietary Micronutrients in Type 2 Diabetes.

Purpose: Differences in metformin effect on glycemic control in type 2 Diabetes (T2D) have been associated with diet, obesity, years since T2D diagnosis and genetic factors, such as the Met408Val (rs628031) SLC22A1/OCT1 gene polymorphism. This study aimed to analyze the effect of metformin and diet on glycemic control and its association with the Met408Val polymorphism in patients with T2D from western Mexico. Patients and Methods: A total of 240 T2D adult patients were enrolled in this cross-sectional study. Anti-hyperglycemic therapy, dietary intake, body composition and glycemic profile were recorded and the determination of genotypes of SLC22A1/OCT1 gene (rs628031) was performed using an allelic discrimination assay. Results: The type of metformin therapy was 47% monotherapy, 45% dual therapy (metformin+glibenclamide or metformin+insulin) and 8% triple therapy (metformin+glibenclamide+insulin). Individuals with metformin monotherapy had a higher glycemic control frequency (%HbA1c <7.0) compared with the dual and triple treatment schemes (77% vs 35% and 15%, respectively; p<0.001). Interestingly, a high potassium intake was documented in the three anti-hyperglycemic therapies and a lower intake of micronutrients, including calcium, magnesium, and zinc. An interaction was found between calcium intake and carriers of the risk allele A (408Val) with %HbA1c (P interaction=0.028), and potassium intake with the TyG index (P interaction=0.027). In addition, there was a positive correlation between calcium intake and %HbA1c (r=0.682; p=0.010), and potassium intake vs TyG index (r=0.593; p=0.033) in risk allele A (408Val) carriers with metformin monotherapy. Genotype frequencies were GG homozygotes (76.6%), GA heterozygotes (21.5%) and AA homozygotes (1.9%). The allele frequency was 87.4% for the ancestral allele G and 12.6% for the risk allele A. Conclusion: These findings suggest a differing effect of metformin on glycemic control regarding calcium and potassium intake and the Met408Val SLC22A1/OCT1 gene polymorphism in T2D patients.

The ACTN3 R577X polymorphism is associated with metabolic alterations in a sex-dependent manner in subjects from western Mexico.

BACKGROUND: The ACTN3 gene is primarily expressed in fast skeletal muscle fibres. A common nonsense polymorphism in this gene is ACTN3 R577X (rs1815739), which causes an absolute deficiency of α-actinin-3 protein and alterations in muscle metabolism. Considering metabolic alterations are influenced by nutrition and genetic factors, as well as lifestyle factors, we hypothesise a possible association of the ACTN3 R577X polymorphism with metabolic alterations. METHODS: In this cross-sectional study, 397 adults met the inclusion criteria. Body composition was measured by electrical bioimpedance. Dietary data were analysed using Nutritionist Pro™ software. Biochemical variables were determined by dry chemistry. Genomic DNA was extracted from peripheral leukocytes and genotyping of the ACTN3 R577X polymorphism was determined by allelic discrimination using TaqMan probes. The statistical analyses were performed using SPSS statistical software. p < 0.05 was considered statistically significant. RESULTS: The ACTN3 577XX genotype was associated with high glucose, triglyceride and very low density lipoprotein-cholesterol levels and a higher frequency of hypertriglyceridaemia and insulin resistance in women. In males, the genetic variant showed a trend towards significance for insulin resistance. CONCLUSIONS: The ACTN3 R577X polymorphism was associated with metabolic alterations in women and a tendency was observed in men variant carriers. Thus, this common genetic variant could be implicated in the development of chronic metabolic diseases.

Impact of APOE Alleles-by-Diet Interactions on Glycemic and Lipid Features- A Cross-Sectional Study of a Cohort of Type 2 Diabetes Patients from Western Mexico: Implications for Personalized Medicine.

PURPOSE: To analyze clinically relevant interactions between the apolipoprotein E (APOE) ε2, ε3 and ε4 alleles and nutritional factors on glycemic control and lipid levels in a cohort of type 2 diabetes (T2D) patients from western Mexico. PATIENTS AND METHODS: In this cross-sectional study of the cohort of T2D patients, a total of 224 individuals were selected for interaction studies. Clinical and anthropometric data were obtained from pre-designed medical records. Dietary intake was assessed by validated three-day food consumption records. Biochemical measurements were determined by automated methods. APOE genotyping was performed by a real-time allelic discrimination assay. Gene-diet interactions were tested by corrected multiple linear regression analyses, which were adjusted by potential confounding factors such as age, sex, energy intake, BMI and anti-hyperglycemic therapy (Metformin, Glibenclamide or Insulin), and years with T2D. RESULTS: Seventy-six percent of patients with T2D were on Metformin therapy. The frequencies of the APOE alleles were ε2 (5.8%), ε3 (74.1%) and ε4 (20.1%). After statistical settings, significant APOE alleles-by-diet interactions in relation to the metabolic profile were found. Interestingly, higher blood levels of total cholesterol (p int. = 0.016), non-HDL-c (p int. = 0.024), and LDL-c (p int. = 0.030) were found only in carriers of the APOE ε2 allele with a low consumption of MUFA. In contrast, carriers of the APOE ε4 allele with a high ω-6:ω-3 PUFA ratio in the diet had higher %HbA1c blood concentrations (p int. = 0.035). CONCLUSION: This study suggests a differential metabolic impact of APOE alleles on lipid/glycemic phenotypes depending on the dietary intake, with important potential implications in the personalized medicine and nutritional management of patients with type 2 diabetes mellitus.

Interactions between DRD2/ANKK1 TaqIA Polymorphism and Dietary Factors Influence Plasma Triglyceride Concentrations in Diabetic Patients from Western Mexico: A Cross-sectional Study.

This study aimed to screen relevant interactions between DRD2/ANKK1 TaqIA polymorphism and dietary intakes with reference to phenotypical features in patients with T2D from western Mexico. In this cross-sectional study, a total of 175 T2D patients were enrolled. Dietary intake was evaluated using 3-day food records and appropriate software. Glycemic and blood lipid profiles were measured by standardized methods. Genotyping of the DRD2/ANKK1 TaqIA polymorphism was performed by the RFLP method. Gene-diet interactions regarding anthropometric and metabolic phenotypes were screened by adjusted multiple linear regression analyses. Genotype frequencies of the DRD2/ANKK1 TaqIA polymorphism were A1A1 (16.0%), A1A2 (52.6%), and A2A2 (31.4%). Statistically significant interactions between the DRD2/ANKK1 TaqIA genotypes and dietary factors in relation to blood triglyceride (TG) levels were found. Carriers of the A1 allele (A1A1 homozygotes plus A1A2 heterozygotes) were protected from TG increases by maltose intake (P int. = 0.023). Instead, A2A2 homozygotes were susceptible to TG rises through consumptions of total fat (P int. = 0.041), monounsaturated fatty acids (P int. = 0.001), and dietary cholesterol (P int. = 0.019). This study suggests that the interactions between DRD2/ANKK1 TaqIA polymorphism and dietary factors (sugar and fats) influence TG levels in diabetic patients.

Association of A-604G ghrelin gene polymorphism and serum ghrelin levels with the risk of obesity in a mexican population.

Obesity is a metabolic disorder that has a multifactorial etiology and affects millions of people worldwide. Ghrelin, a hormone coded by the GHRL gene, plays a role in human body composition and appetite. Single nucleotide polymorphisms (SNPs) of the GHRL gene have been associated with obesity and metabolic disorders. To evaluate the association of A-604G SNP of GHRL promoter region with serum ghrelin levels and the risk of obesity in a Mexican population. Two hundred and fifty individuals were enrolled and classified as obese or control subjects (CS) according to BMI. DNA samples, anthropometric measurements and biochemical parameters were obtained from all subjects. The A-604G SNP was genotyped using PCR-RFLPs technique. Ghrelin levels were measured using a commercial enzyme immunoassay. The G/G genotype was more frequent among obese individuals (p < 0.0001) when compared to CS. The G/A genotype and A allele were associated with protection against obesity (OR 0.29, p < 0.0001; OR 0.39, p < 0.0001 respectively), the A allele remained significant after adjusting for age and gender (OR: 0.25, p < 0.0001). Serum ghrelin levels were higher in obese patients (p = 0.004) than in CS, however, significance was lost after adjustment for age (p = 0.088). The G/G genotype was associated with higher levels of serum ghrelin (p = 0.02) independently of the effect of age. The G/G genotype of the A-604G SNP in the GHRL gene is associated with altered serum ghrelin levels and obesity. The A allele was also associated with protection against obesity in this study.

High frequency of the DRD2/ANKK1 A1 allele in Mexican Native Amerindians and Mestizos and its association with alcohol consumption.

BACKGROUND: Mexico has an ancient tradition of alcohol drinking influenced by genetic and sociocultural factors. This study aimed to determine the distribution of the DRD2/ANKK1 TaqIA polymorphism in Mexican populations and to analyze its association with heavy drinking. METHODS: In a cross-sectional and analytical study, 680 unrelated subjects including two Native Amerindians groups (87 Nahuas and 139 Huicholes), and two Mestizos groups (158 subjects from Tepic, Nayarit and 296 subjects from Guadalajara, Jalisco) were enrolled. DRD2/ANKK1 genotyping was performed by PCR-RFLP and allelic discrimination assays. Genetic analyses were conducted by Arlequin and Structure software. Heavy drinking was defined as ≥300g alcohol/week. The association of the DRD2/ANKK1 TaqIA polymorphism with heavy drinking was estimated. RESULTS: Heavy drinking was prevalent in 64.7% of the study population. The DRD2/ANKK1 A1 allele prevailed in 67% and 65% of Nahuas and Huicholes, respectively and 51% and 47.3% in Mestizos from Tepic and Guadalajara, respectively. Heavy drinking was associated with the A1A1 genotype in the Mestizos of Guadalajara (A1A1 vs. A1A2 OR=4.79, 95%CI 1.81-12.68, p=0.0006; A1A1 vs. A1A2+A2A2, OR=4.09, 95%CI 1.56-10.68, p=0.0021) and in the Mestizos from Tepic (A1A1 vs. A1A2, OR=5.92, 95%CI 2.12-16.49, p=0.0002); A2A2, OR=14.56, 95%CI 3.57-59.24, p=0.00004); A1A2+A2A2, OR=6.68, 95%CI 2.42-18.42, p=0.00005). In Native Amerindians, a lack of association was found. CONCLUSIONS: High frequencies of the DRD2/ANKK1 A1 allele were present in Mexican populations. Native Amerindians exhibited the highest frequencies of the A1 allele documented worldwide to date. The A1A1 genotype was associated with heavy drinking in Mestizos.

Recombinant murine IL-12 promotes a protective Th1/cellular response in Mongolian gerbils infected with Sporothrix schenckii.

Sporotrichosis is a cutaneous fungal infection caused by Sporothrix schenckii. It is known to be mainly contained by Th1 responses. As IL-12 is crucial for Th1 response, we investigated if treatment with recombinant murine IL-12 (rmIL-12) promoted Th1 immunity and/or clinical improvement in an experimental sporotrichosis gerbil model. Gerbils were inoculated with S. schenckii in the footpad and treated with rmIL-12. Seven days post infection there was a significant increase in macrophage phagocytosis and oxidative burst, and in delayed-type hypersensitivity (DTH) reaction in rmIL-12 treated gerbils, as well as a ∼10-fold increase of serum IFN-gamma and a decrease of IL-4 and IL-10. Moreover, rmIL-12 substantially decreased (∼70%) S. schenckii burden in liver and spleen and improved the clinical outcome preventing footpad ulcer and tail nodules observed in untreated gerbils. Our study demonstrates that rmIL-12 promotes Th1 immune response against S. schenckii favouring its clearance and preventing clinical symptoms.

Micronuclei and other nuclear anomalies in exfoliated buccal mucosa cells of Mexican women with breast cancer.

PURPOSE: Breast cancer (BC) is the most frequently diagnosed form of cancer and the leading cause of cancer-related deaths among females in the world. RESULTS of several studies showed that the genome of primary cancer patients (naive for any treatment) is unstable. The purpose of the present study was to evaluate the genomic instability in BC patients by means of buccal cells micronucleus (MN) cytome assay Methods: The frequencies of nuclear anomalies including MN, binucleates (BN), broken eggs (BE), condensed chromatin (CC), karyorrhexis (KR) and karyolysis (KL) were evaluated in exfoliated buccal mucosa cells of Mexican women with primary BC and healthy women. Buccal cells were collected from 21 BC patients (9 with stage I and 12 with stage II) and from 20 healthy females used as control group. RESULTS: The results of the evaluation of cells showed that the frequencies of MN, BN, BE, KR and KL were significantly increased in the pooled group of BC patients compared with the control group. However, no one parameter of buccal MN-cytome assay in patients with stage I BC was significant compared with controls and BC patients with stage II. CONCLUSION: Application of the buccal MN-cytome assay for the study of genomic instability in primary BC patients showed that both genotoxic and cytotoxic effects can be evaluated in such patients.

Alcoholism and liver disease in Mexico: genetic and environmental factors.

Alcoholism and cirrhosis, which are two of the most serious health problems worldwide, have a broad spectrum of clinical outcomes. Both diseases are influenced by genetic susceptibility and cultural traits that differ globally but are specific for each population. In contrast to other regions around the world, Mexicans present the highest drinking score and a high mortality rate for alcoholic liver disease with an intermediate category level of per capita alcohol consumption. Mexico has a unique history of alcohol consumption that is linked to profound anthropological and social aspects. The Mexican population has an admixture genome inherited from different races, Caucasian, Amerindian and African, with a heterogeneous distribution within the country. Thus, genes related to alcohol addiction, such as dopamine receptor D2 in the brain, or liver alcohol-metabolizing enzymes, such as alcohol dehydrogenase class I polypeptide B, cytochrome P450 2E1 and aldehyde dehydrogenase class 2, may vary from one individual to another. Furthermore, they may be inherited as risk or non-risk haplogroups that confer susceptibility or resistance either to alcohol addiction or abusive alcohol consumption and possibly liver disease. Thus, in this era of genomics, personalized medicine will benefit patients if it is directed according to individual or population-based data. Additional association studies will be required to establish novel strategies for the prevention, care and treatment of liver disease in Mexico and worldwide.

Prevalence of hepatitis A, B and C serological markers in children from western Mexico.

INTRODUCTION: Viral hepatitis in children is a major public health problem worldwide. AIM: To evaluate the prevalence of serological markers for hepatitis A, B and C infections in Mexican children diagnosed with hepatitis during a five-year period. MATERIAL AND METHODS: A total of 31,818 children admitted to a tertiary level hospital in Mexico from 2005 to 2009 were evaluated for hepatitis. RESULTS: Hepatitis was found in 215 (0.7%) of the children. Serum samples from hepatitis-positive children were screened for anti-HAV IgM, HBsAg, total anti-HBc and anti-HCV. HAV was the leading cause of viral hepatitis (81%), followed by HBV and HCV (3.1 and 2%, respectively), whereas no serological marker was observed in 13.9% of the analyzed samples. Furthermore, when children were categorized by age, a significant increase in anti-HAV detection was observed in school-aged children (7-11 years old) (p < 0.001) and a reduction in adolescents (12-15 years old). CONCLUSION: In conclusion, hepatitis A is the most prevalent viral hepatitis infection detected in children, followed by HBV and HCV. In addition, the high percentage of hepatitis infections without a known etiological agent and the serological test limitations require the detection of occult HBV, HCV and hepatitis E infections. The age-dependent vulnerability of groups with HAV infections emphasizes the importance of HAV vaccination in young children in Mexico.

Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients

A high prevalence of occult hepatitis B (OHB) genotype H infections has been observed in the native Mexican Nahua population. In addition, a low incidence of hepatitis B virus (HBV)-associated hepatocellular carcinoma has been described in Mexico. The immune response to infection among OHB-infected patients has been poorly evaluated in vivo. Therefore, we assessed the expression profiles of 23 cytokines in OHB genotype H-infected Nahua patients. A total of 41 sera samples from natives of the Nahua community were retrospectively analysed. Based on their HBV antibody profiles, patients were stratified into two groups: OHB patients (n = 21) and patients that had recovered from HBV infection (n = 20). Herein, we report distinctive cytokines profiles in OHB-infected individuals. Compared to healthy controls (n = 20) and patients who resolved HBV infection, OHB-infected patients displayed an increase in interleukin (IL)-2 secretion in addition to a characteristic inflammation profile (decrease in IL-8 and tumour necrosis factor-alpha levels and increased levels of tumour growth factor-beta). IL-15 and interferon-gamma levels were reduced in OHB-infected individuals when compared to those patients who resolved HBV infection. In contrast, OHB patients showed an increase in monocyte chemoattractant protein (MCP)-1 and MCP-2 compared to healthy controls and patients who resolved HBV infection. These findings suggest that cytokine expression can influence the severity of OHB disease and could lead to new investigation into the treatment of liver and other infectious diseases.

[Epidemiology of viral hepatitis in Mexico]. / Epidemiología de las hepatitis virales en México.

The main etiology of liver disease in Mexico is alcohol and viral hepatitis. The aim of the present study was to analyze the current epidemiology of viral hepatitis in Mexico. From 2000 to 2007 the Ministry of Health reported 192 588 cases of hepatitis, 79% HAV, 3.3% HBV, 6% HCV, and 12% without a specific etiologic factor. Due to high endemic areas for HBV infection in native Mexican population, limitations in the diagnostic sensitivity and specificity of the serological immunoassays used to date and presence of occult hepatitis B in the country, the real prevalence of HBV infection could be even higher than HCV in Mexico. Hepatitis E virus in cirrhotic patients and in porcine farms could at least partially explain the cases of hepatitis that are diagnosed without a specific etiologic agent. Specific strategies to establish control regulations against viral hepatitis infections in Mexico are proposed.

Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients.

A high prevalence of occult hepatitis B (OHB) genotype H infections has been observed in the native Mexican Nahua population. In addition, a low incidence of hepatitis B virus (HBV)-associated hepatocellular carcinoma has been described in Mexico. The immune response to infection among OHB-infected patients has been poorly evaluated in vivo. Therefore, we assessed the expression profiles of 23 cytokines in OHB genotype H-infected Nahua patients. A total of 41 sera samples from natives of the Nahua community were retrospectively analysed. Based on their HBV antibody profiles, patients were stratified into two groups: OHB patients (n = 21) and patients that had recovered from HBV infection (n = 20). Herein, we report distinctive cytokines profiles in OHB-infected individuals. Compared to healthy controls (n = 20) and patients who resolved HBV infection, OHB-infected patients displayed an increase in interleukin (IL)-2 secretion in addition to a characteristic inflammation profile (decrease in IL-8 and tumour necrosis factor-alpha levels and increased levels of tumour growth factor-beta). IL-15 and interferon-gamma levels were reduced in OHB-infected individuals when compared to those patients who resolved HBV infection. In contrast, OHB patients showed an increase in monocyte chemoattractant protein (MCP)-1 and MCP-2 compared to healthy controls and patients who resolved HBV infection. These findings suggest that cytokine expression can influence the severity of OHB disease and could lead to new investigation into the treatment of liver and other infectious diseases.

Epidemiología de las hepatitis virales en México / Epidemiology of viral hepatitis in Mexico

Las hepatitis virales son una de las causas principales de daño hepático en México. En este estudio se analiza el estado actual de las hepatitis virales en México. La Secretaría de Salud informa un total de 192 588 casos de hepatitis virales entre 2000 y 2007. De éstos, 79 por ciento corresponden aVHA, 3.3 por ciento aVHB, 6 por ciento a VHC y 11.7 por ciento a casos sin agente etiológico descrito. No obstante, el VHB se podría estar subdiagnosticando, ya que hay zonas de alta endemia en poblaciones indígenas, existen limitaciones en la sensibilidad y especificidad de las pruebas inmunológicas y podría ser común la hepatitis B oculta. ElVHE podría ser uno de los agentes etiológicos de aquellos casos que carecen de un agente etiológico conocido. Se proponen estrategias específicas para el control de las hepatitis virales tendientes a disminuir el número de casos.

The main etiology of liver disease in Mexico is alcohol and viral hepatitis. The aim of the present study was to analyze the current epidemiology of viral hepatitis in Mexico. From 2000 to 2007 the Ministry of Health reported 192 588 cases of hepatitis, 79 percent HAV, 3.3 percent HBV, 6 percent HCV, and 12 percent without a specific etiologic factor. Due to high endemic areas for HBV infection in native Mexican population, limitations in the diagnostic sensitivity and specificity of the serological immunoassays used to date and presence of occult hepatitis B in the country, the real prevalence of HBV infection could be even higher than HCV in Mexico. Hepatitis E virus in cirrhotic patients and in porcine farms could at least partially explain the cases of hepatitis that are diagnosed without a specific etiologic agent. Specific strategies to establish control regulations against viral hepatitis infections in Mexico are proposed.

Polymorphisms of alcohol metabolizing enzymes in indigenous Mexican population: unusual high frequency of CYP2E1*c2 allele.

BACKGROUND: Alcohol abuse represents the major identified etiological factor of cirrhosis in México. ADH1B, ALDH2, and CYP2E1 have been considered candidate genes in alcohol-related diseases. Controversial results probably due to ethnic differences, among other factors, have been reported. Mexican Mestizos (MES) derive from the combination of indigenous, Spaniard, and African genes. Huichols (HUI) constitute an indigenous group from western Mexico with no racial admixture. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy HUI and MES from western Mexico. Lipid and hepatic profile were also carried out. METHODS: One hundred and one HUI and 331 MES subjects were studied. Genotype and allele frequency were assessed through polymerase chain reaction-restriction fragment length polymorphism after DNA isolation from peripheral leukocytes. Commercial kits for lipid and hepatic determinations were used. RESULTS: Polymorphic allele distribution in HUI was: 0%ADH1B*2, 0.5%ALDH2*2, 51.5%CYP2E1*c2; in MES: 3.4%ADH1B*2, 0%ALDH2*2, 16.1%CYP2E1*c2. Frequency of ADH1B*2 was statistically (p < 0.001) lower in HUI than MES. CYP2E1*c2 polymorphic allele was significantly higher (p < 0.0001) in HUI than MES. Hepatic profile was normal in both groups. HUI showed a better lipid profile than MES independently of genotype. CONCLUSIONS: Huichols exhibited the highest CYP2E1*c2 allele frequency of the world documented up to this date; meanwhile, ADH1B*2 and ALDH2*2 were practically absent. This feature could be useful in the understanding of Mexican population gene composition, alcohol metabolism, and alcoholic liver disease development. However, further association studies are necessary. The heterogeneity of Mexican population was evidenced by the significantly different distribution of CYP2E1*c2 allele observed among different regions of the country. Lipid and hepatic values were not associated to genotype. This report constitutes the first study dealing with gene polymorphisms of alcohol metabolizing enzymes conducted in HUI.