RESUMO

Glucose and lipid metabolism regulation by the peroxisome proliferator-activated receptors (PPARs) has been extensively reported. However, the role of their polymorphisms remains unclear. OBJECTIVE: To determine the relation between PPAR-γ2 rs1801282 (Pro12Ala) and PPAR-ß/δ rs2016520 (+294T/C) polymorphisms and metabolic biomarkers in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: We included 314 patients with T2D. Information on anthropometric, fasting plasma glucose (FPG), HbA1c and lipid profile measurements was taken from clinical records. Genomic DNA was obtained from peripheral blood. End-point PCR was used for PPAR-γ2 rs1801282, while for PPAR-ß/δ rs2016520 the PCR product was digested with Bsl-I enzyme. Data were compared with parametric or non-parametric tests. Multivariate models were used to adjust for covariates and interaction effects. RESULTS: minor allele frequency was 12.42% for PPAR-γ2 rs1801282-G and 13.85% for PPAR-ß/δ rs2016520-C. Both polymorphisms were related to waist circumference; they showed independent effects on HbA1c, while they interacted for FPG; carriers of both PPAR minor alleles had the highest values. Interactions between FPG and polymorphisms were identified in their relation to triglyceride level. CONCLUSIONS: PPAR-γ2 rs1801282 and PPAR-ß/δ rs2016520 polymorphisms are associated with anthropometric, glucose, and lipid metabolism biomarkers in T2D patients. Further research is required on the molecular mechanisms involved.

Assuntos

Diabetes Mellitus Tipo 2 , PPAR delta , PPAR beta , Adulto , Humanos , PPAR gama/genética , PPAR delta/genética , Diabetes Mellitus Tipo 2/genética , PPAR beta/genética , Hemoglobinas Glicadas/genética , Polimorfismo de Nucleotídeo Único , Biomarcadores , Glucose

RESUMO

The WHO identifies high BMI, high blood pressure, and high fasting plasma glucose as chronic disease risk factors, whereas physical fitness is identified as a protective behavioral factor. This study responds to the rising interest in assessing metabolic factors and physical activity within young populations of Mestizo, Tarahumara, and Mennonite from Chihuahua Mexico, due to its strong relationship with disease development and low well-being. A cross-sectional study was conducted with 201 teenagers from rural towns in Northern Mexico, and relationships between physical fitness and cardio-metabolic risk related to anthropometric, glycolipid, and vascular function factors were assessed. ANOVA-tested differences among ethnic groups using physical fitness as a grouping variable and measures of cardio-metabolic risks were used as dependent variables. A stepwise regression analysis allowed us to identify the best predictors for physical fitness. Clinical risk factors were analyzed by ethnic group and sex. No differences were found among ethnic groups in physical fitness and cardio-metabolic health risks; sex differentiated higher health risks related to behavioral factors, since young women showed lower physical fitness across ethnicities. Clinically, the Mestizo sample showed higher numbers of individuals with one risk factor. Mennonites showed a high frequency of anthropometric and fitness health risks with low glycolipid and vascular risks. Tarahumara had fewer risk factors as compared with both Mestizo and Mennonite. Rural populations are harder to reach, both for health assessment and intervention; health professionals must work close to local community organizations to gain access.

Assuntos

Hipertensão , Aptidão Física , Humanos , Adolescente , Feminino , México , Estudos Transversais , Glicolipídeos

RESUMO

We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals.

RESUMO

Peroxisome proliferator-activated receptors (PPARs) play roles in glucose and lipid metabolism regulation. Pro12Ala PPAR-γ2 and +294T/C PPAR-δ have been associated with dyslipidemia, hyperglycemia and high body mass index (BMI). We compared metabolic traits and determined associations with Pro12Ala PPAR-γ2 or +294T/C PPAR-δ polymorphism among teenagers from different ethnicity. Four hundred and twelve samples with previous biochemical and biometric measurements were used. Genomic DNA from peripheral blood was extracted and analyzed by end-point PCR for Pro12Ala PPAR-γ2. The +294T/C PPAR-δ PCR product was also digested with Bsl I. Two genotype groups were formed: major allele homozygous and minor allele carriers. Pro12Ala PPAR-γ2 G minor allele frequencies were: 10% in Mestizo-1, 19% in Mestizo-2, 23% in Tarahumara, 12% in Mennonite, and 17% in the total studied population. The +294T/C PPAR-δ C minor allele frequencies were: 18% in Mestizo-1, 20% in Mestizo-2, 6% in Tarahumara, 13% in Mennonite, and 12% in the total studied population. Teenagers with PPAR-γ2 G allele showed a greater risk for either high waist/height ratio or low high-density lipoprotein; and, also had lower total cholesterol. Whereas, PPAR-γ2 G allele showed lower overweight/obesity phenotype (BMI Z-score) frequency, PPAR-δ C allele was a risk factor for it. Metabolic traits were associated with both PPAR polymorphisms.

Assuntos

Peso Corporal/genética , Colesterol/genética , Lipoproteínas HDL/genética , PPAR delta/genética , PPAR gama/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Colesterol/sangue , Feminino , Frequência do Gene , Humanos , Lipoproteínas HDL/sangue , Masculino , México , Mutação de Sentido Incorreto

RESUMO

Objective: To evaluate the morphology of the placenta in patients with pregestational overweight (OW), pregestational obesity (PGOB), or normal weight.Methods: A cross-sectional study including women (n = 114) ≥20 years of age with a singleton pregnancy was carried out. The groups were integrated according to pregestational body mass index (BMI): 51 patients had a normal BMI (18.5-24.99 kg/m2), 30 were overweight (25-29.99 kg/m2), and 33 women were obese (≥30.0 kg/m2). A morphometric study of the placenta was performed and the placental maturity index (PMI) was calculated according to the formula: PMI = number of vasculo-syncytial membranes (VSM) in 1 mm2/VSM thickness. In the histopathological study, the presence of infarcts, calcifications, hemorrhage, thrombosis, fibrosis, cysts, and edema was determined.Results: The weight and length of newborns at birth were greater in the group with PGOB (p < .01). We observed a lower number of VSM (29 ± 9 versus 39 ± 13 and 34 ± 11) and a greater thickness (1.05 ± 0.24 versus 0.95 ± 0.08 and 0.89 ± 0.09) and, therefore, a lower PMI (29.75 ± 12.63 versus 40.88 ± 15.25 and 39.28 ± 14.4) in the group of women with PGOB compared with the group of women with OW or normal weight (p < .01). The histopathological analyses showed a greater frequency of edema and cysts in the PGOB group.Conclusion: PGOB is associated with a higher placental weight and newborn weight, a lower PMI, and the presence of histopathological alterations. The preceding points highlight the importance of promoting an appropriate pregestational weight in women of reproductive age.

Assuntos

Obesidade , Placenta , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso , Gravidez

RESUMO

Abstract The GSTT1 and GSTM1 genes are key molecules in cellular detoxification. Null variants in these genes are associated with increase susceptibility to developing different types of cancers. The aim of this study was to determine the prevalence of GSTT1 and GSTM1 null genotypes in Mestizo and Amerindian individuals from the Northwestern region of Mexico, and to compare them with those reported worldwide. GSTT1 and GSTM1 null variants were genotyped by multiplex PCR in 211 Mestizos and 211 Amerindian individuals. Studies reporting on frequency of GSTT1 and GSTM1 null variants worldwide were identified by a PubMed search and their geographic distribution were analyzed. We found no significant differences in the frequency of the null genotype for GSTT1 and GSM1 genes between Mestizo and Amerindian individuals. Worldwide frequencies of the GSTT1 and GSTM1 null genotypes ranges from 0.10 to 0.51, and from 0.11 to 0.67, respectively. Interestingly, in most countries the frequency of the GSTT1 null genotype is common or frequent (76%), whereas the frequency of the GSMT1 null genotype is very frequent or extremely frequent (86%). Thus, ethnic-dependent differences in the prevalence of GSTT1 and GSTM1 null variants may influence the effect of environmental carcinogens in cancer risk.

RESUMO

The GSTT1 and GSTM1 genes are key molecules in cellular detoxification. Null variants in these genes are associated with increase susceptibility to developing different types of cancers. The aim of this study was to determine the prevalence of GSTT1 and GSTM1 null genotypes in Mestizo and Amerindian individuals from the Northwestern region of Mexico, and to compare them with those reported worldwide. GSTT1 and GSTM1 null variants were genotyped by multiplex PCR in 211 Mestizos and 211 Amerindian individuals. Studies reporting on frequency of GSTT1 and GSTM1 null variants worldwide were identified by a PubMed search and their geographic distribution were analyzed. We found no significant differences in the frequency of the null genotype for GSTT1 and GSM1 genes between Mestizo and Amerindian individuals. Worldwide frequencies of the GSTT1 and GSTM1 null genotypes ranges from 0.10 to 0.51, and from 0.11 to 0.67, respectively. Interestingly, in most countries the frequency of the GSTT1 null genotype is common or frequent (76%), whereas the frequency of the GSMT1 null genotype is very frequent or extremely frequent (86%). Thus, ethnic-dependent differences in the prevalence of GSTT1 and GSTM1 null variants may influence the effect of environmental carcinogens in cancer risk.

RESUMO

Studies of gene-environment (GxE) interactions describe how genetic and environmental factors influence the risk of developing disease. Intermediate (molecular or clinical) phenotypes (IPs) are traits or metabolic biomarkers that mediate the effects of gene-environment influences on risk behaviors. Functional systems genomics discovery offers mechanistic insights into how DNA variations affect IPs in order to detect genetic causality for a given disease. Disorders of body composition include obesity (OB), Type 2 diabetes (T2D), and osteoporosis (OSTP). These pathologies are examples of how a GxE interaction contributes to their development. IPs as surrogates for inherited genotypes play a key role in models of genetic and environmental interactions in health outcomes. Such predictive models may unravel relevant genomic and molecular pathways for preventive and therapeutic interventions for OB, T2D, and OSTP. Annotation strategies for genomes, in contrast to phenomes, are well advanced. They generally do not measure specific aspects of the environment. Therefore, the concepts of deep phenotyping and the exposome generate new avenues to exploit with high-resolution technologies for analyzing this sophisticated phenome. With the successful characterization of phenomes, exposomes, and genomes, environmental and genetic determinants of chronic diseases can be united with multi-OMICS studies that better examine GxE interactions.

Assuntos

Diabetes Mellitus Tipo 2/genética , Interação Gene-Ambiente , Obesidade/genética , Osteoporose/genética , Fenótipo , Composição Corporal , Humanos

RESUMO

Tuberculosis (TB) and its co-morbid conditions have become a burden on global health economies. It is well understood that susceptibility of the host to TB infection/disease is influenced by both genetic and environmental factors and their interactions. The aims of this pilot case-control study are to characterize the sociodemographic and environmental factors related to active TB disease (TB/case) and latent TB infection (LTBI/control) status, and to identify risk factors associated with progression from LTBI to TB. We recruited 75 cases with TB (mean age=46.3y; females=41%) and 75 controls with LTBI (mean age=39.0y; females=37%), from the Mestizo population of Cuidad Juárez, Mexico. In addition to the determination of case/control status, information on environmental variables was collected (e.g., socioeconomic status, smoking, alcohol consumption, substance abuse, nutritional status, household demographics, medical histories and presence of type 2 diabetes [T2DM]). The data were analyzed to identify the environmental correlates of TB and LTBI using univariate and multivariate statistical approaches. Following multivariate logistic regression analysis, TB was associated with poor nutrition, T2DM, family history of TB, and non-Chihuahua state of birth. These preliminary findings have relevance to TB control at the Mexico-United States border, and contribute to our future genetic study of TB in Mexicans.

Assuntos

Diabetes Mellitus Tipo 2/epidemiologia , Emigração e Imigração/estatística & dados numéricos , Desnutrição/epidemiologia , Mycobacterium tuberculosis/isolamento & purificação , Fumar/epidemiologia , Tuberculose/epidemiologia , Adulto , Antituberculosos/uso terapêutico , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Características da Família , Feminino , Predisposição Genética para Doença/epidemiologia , Humanos , Imunidade Inata , Tuberculose Latente/epidemiologia , Masculino , Desnutrição/complicações , México/epidemiologia , Projetos Piloto , Fatores de Risco , Fumar/efeitos adversos , Inquéritos e Questionários

RESUMO

The compartment syndrome is a condition characterized by a raised hydraulic pressure within a closed and non expandable anatomical space. It leads to a vascular insufficiency that becomes critical once the vascular flow cannot return the fluids back to the venous system. This causes a potential irreversible damage of the contents of the compartment, especially within the muscle tissues. Gluteal compartment syndrome (GCS) secondary to hematomas is seldom reported. Here we present a case of a 51-year-old patient with history of a non-Hodgkin lymphoma who underwent a bone marrow aspiration from the posterior iliac crest that had excessive bleeding at the puncture zone. The patient complained of increasing pain, tenderness, and buttock swelling. Intraoperative pressure validation of the gluteal compartment was performed, and a GCS was diagnosed. The patient was treated with a gluteal region fasciotomy. The patient recovered from pain and swelling and was discharged shortly after from the hospital. We believe clotting and hematologic disorders are a primary risk factor in patients who require bone marrow aspirations or biopsies. It is important to improve awareness of GCS in order to achieve early diagnosis, avoid complications, and have a better prognosis.