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.

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.