RESUMO
This is a longitudinal single-arm clinical trial aimed to investigate whether exercise training would modify the whole blood methylation profile in healthy women. A total of 45 subjects were engaged in an exercise training protocol during a 14-wk follow up, consisting of aerobic cardiorespiratory and muscle strength exercises. Subjects were evaluated at baseline (PRE), after 7 wk of exercise training (POST 7), and after 14 wk of exercise training (POST 14). Functional primary outcomes included anthropometric, blood pressure, biochemical measurements, physical tests, and global health assessments. Blood samples were collected at each time point to determine the methylation profile using a DNA methylation array technique screening up to 850k different sites. Exercise training decreased blood pressure and triglyceride levels and enhanced physical performance, including upper- and lower-body maximum strength. Moreover, exercise training improved markers of quality of life. In the array analysis, 14 wk of exercise training changed the methylation of more than 800 sites. Across these differentially methylated sites, we found that differentially methylated sites in the promoter region were more hypermethylated after exercise training, suggesting that this hypermethylation process may affect the transcription process. When inputting the differentially methylated sites in pathway analysis, we found several metabolic pathways, including AMPK signaling, TGF-ß signaling, and insulin signaling. This study demonstrates that exercise training promotes a robust change in the whole blood methylation profile and provides new insights into the key regulators of exercise-induced benefits.NEW & NOTEWORTHY We have shown that exercise training lowers blood pressure and triglyceride levels, improves physical performance, and improves quality of life in middle-aged and elderly women. Regarding epigenetic data, we noticed that more than 800 sites are differentially methylated in whole blood after physical training. We emphasize that the differentially methylated sites in the promoter region are more hypermethylated after physical training. In addition, this study shows that key members of metabolic pathways, including AMPK signaling, TGF-ß signaling, and insulin signaling, are among the genes hypermethylated after physical exercise in older women.
Assuntos
Insulinas , Treinamento Resistido , Idoso , Pessoa de Meia-Idade , Humanos , Feminino , Metilação de DNA , Qualidade de Vida , Proteínas Quinases Ativadas por AMP , Exercício Físico/fisiologia , Triglicerídeos , Insulinas/genética , Fator de Crescimento Transformador beta , Treinamento Resistido/métodosRESUMO
Haplotype 46/1 (GGCC) consists of a set of genetic variations distributed along chromosome 9p.24.1, which extend from the Janus Kinase 2 gene to Insulin like 4. Marked by four jointly inherited variants (rs3780367, rs10974944, rs12343867, and rs1159782), this haplotype has a strong association with the development of BCR-ABL1-negative myeloproliferative neoplasms (MPNs) because it precedes the acquisition of the JAK2V617F variant, a common genetic alteration in individuals with these hematological malignancies. It is also described as one of the factors that increases the risk of familial MPNs by more than five times, 46/1 is associated with events related to inflammatory dysregulation, splenomegaly, splanchnic vein thrombosis, Budd-Chiari syndrome, increases in RBC count, platelets, leukocytes, hematocrit, and hemoglobin, which are characteristic of MPNs, as well as other findings that are still being elucidated and which are of great interest for the etiopathological understanding of these hematological neoplasms. Considering these factors, the present review aims to describe the main findings and discussions involving the 46/1 haplotype, and highlights the molecular and immunological aspects and their relevance as a tool for clinical practice and investigation of familial cases.
Assuntos
Insulinas , Transtornos Mieloproliferativos , Neoplasias , Humanos , Janus Quinase 2/genética , Haplótipos , Transtornos Mieloproliferativos/genética , Suscetibilidade a Doenças , Insulinas/genética , MutaçãoRESUMO
Obesity is one of the main public health problems in Mexico and the world and one from which a large number of pathologies derive. Single nucleotide polymorphisms (SNPs) of various genes have been studied and proven to contribute to the development of multiple diseases. SNPs of the leptin pathway have been associated with the control of hunger and energy expenditure as well as with obesity and type 2 diabetes mellitus. Therefore, the present work focused on determining the association between anthropometric markers and biochemical and dietary factors related to obesity and SNPs of leptin pathway genes, such as the leptin gene (LEP), the leptin receptor (LEPR), proopiomelanocortin (POMC), prohormone convertase 1 (PCSK1), and the melanocortin 4 receptor (MC4R). A population of 574 young Mexican adults of both sexes, aged 19 years old on average and without metabolic disorders previously diagnosed, underwent a complete medical and nutritional evaluation, biochemical determination, and DNA extraction from the blood; DNA samples were subsequently genotyped. Association analyses between anthropometric, biochemical, and dietary variables with SNPs were performed using binary logistic regressions (p-value = 0.05). Although the sampled population did not have previously diagnosed diseases, the evaluation results showed that 33% were overweight or obese according to BMI and 64% had non-clinically elevated levels of body fat. From the 74 SNP markers analyzed from the five previously mentioned genes, 62 showed polymorphisms within the sampled population, and only 35 of these had significant associations with clinical variables. The risk associations (OR > 1) occurred between clinical markers with elevated values for waist circumference, waist−height index, BMI, body fat percentage, glucose levels, insulin levels, HOMA-IR, triglyceride levels, cholesterol levels, LDL-c, low HDL-c, carbohydrate intake, and protein intake and SNPs of the LEP, LEPR, PCSK1, and MC4R genes. On the other hand, the protective associations (OR < 1) were associated with markers including elevated values for insulin, HOMA-IR, cholesterol, c-LDL, energy intake > 2440 Kcal/day, and lipid intake and SNPs of the LEP and LEPR genes and POMC. The present study describes associations between SNPs in leptin pathway genes, revealing positive and negative interactions between reported SNPs and the clinical markers related to obesity in a sampled Mexican population. Hence, our results open the door for the further study of new genetic variants and their influence on obesity.
Assuntos
Diabetes Mellitus Tipo 2 , Insulinas , Biomarcadores , Colesterol , Dieta , Feminino , Humanos , Insulinas/genética , Leptina/genética , Masculino , Obesidade/epidemiologia , Polimorfismo de Nucleotídeo Único , Pró-Opiomelanocortina/genética , Adulto JovemRESUMO
BACKGROUND: The aging process causes physiological changes on its own. The combination of an unhealthy lifestyle with the presence of genetic polymorphisms, such as the Val16Ala of the antioxidant enzyme manganese-dependent superoxide dismutase (MnSOD) may contribute to a greater occurrence of cardiometabolic risk factors. OBJECTIVE: This study aimed to verify the association of Val16Ala-MnSOD polymorphism with food intake, caloric expenditure, and cardiometabolic risk factors in the elderly. METHODS: A cross-sectional study with a sample size of 270 elderly individuals assisted in primary health care in the city of Porto Alegre, RS, Brazil. Val16Ala polymorphism, glucose, lipid profile, insulin, HOMA-IR, blood pressure, waist circumference, PCR-us, IL-6, food consumption, and caloric expenditure were evaluated. RESULTS: The average age of the elderly was 68.6 ± 7.6 years. There were statistically significant differences regarding the consumption of two or more servings of fruits and vegetables daily between the elderly VV versus AV (P=0.017). There were also statistically significant differences regarding the consumption of two or more daily servings of legumes and eggs between the elderly AA versus VV (P=0.002). The median of insulin was higher in the elderly AA versus AV (P=0.025) and the median of HOMA-IR was higher in the elderly VV versus AV (P=0.029). AA elderly individuals had higher means of high-density lipoprotein (HDL-c), compared to AV (P=0.029). CONCLUSION: The results suggest that Val16Ala -MnSOD polymorphism is associated with the consumption of fruits, vegetables, legumes, and eggs, as well as with cardiometabolic risk factors in the elderly.
Assuntos
Fatores de Risco Cardiometabólico , Insulinas , Idoso , Estudos Transversais , Ingestão de Alimentos , Humanos , Insulinas/genética , Polimorfismo Genético , Atenção Primária à Saúde , Superóxido DismutaseRESUMO
Samoyeds and Australian Terriers are the 2 dog breeds at highest risk (>10-fold) for diabetes mellitus in the United States. It is unknown if the insulin (INS) gene is involved in the pathophysiology of diabetes in Samoyeds and Australian Terriers. It was hypothesized that the INS gene region provides a common genetic causality for diabetes in Samoyeds and Australian Terriers. We conducted a 2-stage genetic association study involving both breeds. In the discovery stage (Stage 1), Samoyeds with and without diabetes were compared in the frequencies of 447 tagging single-nucleotide polymorphisms (SNPs) within 2.5 megabases (Mb) up- and downstream of the INS gene on the Illumina CanineHD BeadChip. SNPs yielding a P-value < 0.005 were selected for further follow-up. In the validation stage (Stage 2), Australian Terriers with and without diabetes were compared in the SNPs genotyped by the Affymetrix GeneChip Canine Genome 2.0 Array and within 1 Mb up- and downstream of the selected SNPs from Stage 1. Two SNPs that were in high linkage disequilibrium (LD, r2 = 0.7) were selected from Stage 1. In Stage 2, among the 76 SNPs examined, 5 were significantly associated with diabetes after Bonferroni's correction for multiple comparisons. Three of these 5 SNPs were in complete LD (r2 = 1 for all associations) and the 2 remaining SNPs were in moderate LD (r2 = 0.4). In conclusion, an association between the INS gene region and diabetes was suggested in 2 dog breeds of different clades. This region could have importance in diabetes in other breeds or in canine diabetes at large.