Wilson Araújo da Silva Júnior

Who were the male founders of rural Brazilian Afro-derived communities? A proposal based on three populations

Background: Brazilian Quilombos are Afro-derived communities founded mainly by fugitive slaves between the 16th and 19th centuries; they can be recognized today by ancestral and cultural characteristics. Each of these remnant communities, however, has its own particular history, which includes the migration of non-African derived people. Methods: The present work presents a proposal for the origin of the male founder in Brazilian quilombos based on Y-haplogroup distribution. Y haplogroups, based on 16 binary markers (92R7, SRY2627, SRY4064, SRY10831.1 and .2, M2, M3, M09, M34, M60, M89, M213, M216, P2, P3 and YAP), were analysed for 98 DNA samples from genetically unrelated men from three rural Brazilian Afro-derived communities—Mocambo, Rio das Rãs and Kalunga—in order to estimate male geographic origin. Results: Data indicated significant differences among these communities. A high frequency of non-African haplogroups was observed in all communities. Conclusions: This observation suggested an admixture process that has occurred over generations and directional mating between European males and African female slaves that must have occurred on farms before the slaves escaped. This means that the admixture occurred before the slaves escaped and the foundation of the quilombo.

Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries.

BackgroundLynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected Lynch syndrome.MethodsBlood samples from 88 patients were analyzed through sequencing MLH1, MSH2 and MSH6 genes. The probability of detecting a mutation was calculated using the PREMM, Barnetson, MMRpro, Wijnen and Myriad models. To evaluate the sensitivity and specificity of the models, receiver operating characteristic curves were constructed.ResultsOf the 88 patients included in this analysis, 31 mutations were identified: 16 were found in the MSH2 gene, 15 in the MLH1 gene and no pathogenic mutations were identified in the MSH6 gene. It was observed that the AUC for the PREMM (0.846), Barnetson (0.850), MMRpro (0.821) and Wijnen (0.807) models did not present significant statistical difference. The Myriad model presented lower AUC (0.704) than the four other models evaluated. Considering thresholds of ≥ 5%, the models sensitivity varied between 1 (Myriad) and 0.87 (Wijnen) and specificity ranged from 0 (Myriad) to 0.38 (Barnetson).ConclusionsThe Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models.

UCP1 and UCP3 Expression Is Associated with Lipid and Carbohydrate Oxidation and Body Composition

Background/Objective Uncoupling proteins (UCPs) are located in the inner membrane of mitochondria. These proteins participate in thermogenesis and energy expenditure. This study aimed to evaluate how UCP1 and UCP3 expression influences substrate oxidation and elicits possible changes in body composition in patients submitted to bariatric surgery. Subjects/Methods This is a longitudinal study comprising 13 women with obesity grade III that underwent bariatric surgery and 10 healthy weight individuals (control group). Body composition was assessed by bioelectrical impedance. Carbohydrate and fat oxidation was determined by indirect calorimetry. Subcutaneous adipose tissue was collected for gene expression analysis. QPCR was used to evaluate UCP1 and UCP3 expression. Results Obese patients and the control group differed significantly in terms of lipid and carbohydrate oxidation. Six months after bariatric surgery, the differences disappeared. Lipid oxidation correlated with the percentage of fat mass in the postoperative period. Multiple linear regression analysis showed that the UCP1 and UCP3 genes contributed to lipid and carbohydrate oxidation. Additionally, UCP3 expression was associated with BMI, percentage of lean body mass, and percentage of mass in the postoperative period. Conclusions UCP1 and UCP3 expression is associated with lipid and carbohydrate oxidation in patients submitted to bariatric surgery. In addition, UCP3 participates in body composition modulation six months postoperatively.

UCP1 -3826 A>G polymorphism affects weight, fat mass, and risk of type 2 diabetes mellitus in grade III obese patients

OBJECTIVE We investigated whether or not the UCP1 -3826 A>G polymorphism is associated with obesity and related metabolic disorders in grade III obese patients. METHODS 150 obese patients (body mass index ≥35 kg/m(2)) who were candidates for bariatric surgery were studied. Weight (kg), body mass index (kg/m(2)); fat free mass (kg), fat mass (kg), energy intake (kcal), level of physical activity, plasma levels of glucose, total cholesterol, low-density lipoprotein, high-density lipoprotein (HDL), triacylglycerols, and the prevalence of comorbidities associated with obesity were collected from medical records. Polymorphism rs1800592 genotyping was performed through allelic discrimination method in real time polymerase chain reaction using the TaqMan predesigned SNP Genotyping Assays kits. The t test was done to determine if genotypes of each polymorphism are associated with anthropometric and body composition variables. Linear regression models were used for age, sex, height, physical activity, and energy intake in weight and body composition variations (P < 0.05). RESULTS Among these 150 individuals (47.2 ± 10.5 y, 80% women) the distribution of AA, AG, and GG was 41.3%, 45.3%, and 13.4%, respectively. Weight and body fat were lower in individuals who were carriers of a mutated allele G. It was observed that mutated homozygotes (GG) had a lower frequency of type 2 diabetes mellitus compared with those of wild allele (AA+AG). CONCLUSIONS UCP1 -3826 A>G polymorphism is associated with weight, body fat mass, and risk of type 2 diabetes mellitus in obese individuals candidates for bariatric surgery.

ANXA1(Ac2-26) peptide, a possible therapeutic approach in inflammatory ocular diseases

The eye is immunologically privileged when inflammatory responses are suppressed. One component responsible for the suppression of inflammatory responses is the blood retinal barrier, which comprises the retinal pigment epithelium. The destruction of this barrier initiates inflammation, which can affect any part of the eye. Therefore, inflammatory response is controlled by the action of anti-inflammatory mediators, among these mediators, annexin A1 (ANXA1) protein acts as a modulator of inflammation. In this study we aimed to improve the knowledge of this area by investigating how a peptide of the ANXA1 protein (ANXA1Ac2-26) modulates the morphology, proliferation, migration and expression of genes and proteins in human retinal pigment epithelium cells (ARPE-19). Determining how signaling pathways (NF-κB and UBC) are modulated by the ANXA1Ac2-26 peptide could be important for understanding the inflammatory process. ARPE-19 cells were activated by bacterial lipopolysaccharide endotoxin (LPS) and treated with ANXA1Ac2-26 peptide, in a concentration of 1.7μM and 33.8μM. We observed that the LPS activation diminished the levels of endogenous ANXA1 after 2h and 24h and ANXA1Ac2-26 peptide decreased the proliferation and re-establishes the migration of ARPE-19 cells. After using a hybridization approach, 80 differentially expressed genes were found. Five of these genes were selected (LRAT, CTGF, MAP1B, ALDH1A3 and SETD7) and all were down-regulated after treatment with the peptide. The genes CTGF and LRAT would be considered as potential molecular markers of ophthalmologic inflammation. The expression of pro-inflammatory cytokines was also decreased after the treatment, indicating the efficiency of the anti-inflammatory peptide at high concentrations, since the reduction in the levels of these mediators were observed after the treatment with ANXA1Ac2-26 peptide at 33.8μM. Our results suggest that the retinal pigment epithelial cells are a potential target of the ANXA1 protein and point to possible applications of the ANXA1Ac2-26 peptide as an innovative therapy for the treatment of ocular inflammation.

The Genetic Predisposition Score of Seven Obesity-Related Single Nucleotide Polymorphisms Is Associated with Better Metabolic Outcomes after Roux-en-Y Gastric Bypass

Background/Aims: Genetic variants associated with obesity have cumulative effects on obesity risk and related phenotypes. This study aimed to estimate the contribution of a genetic predisposition score (GPS) calculated from 7 obesity-related polymorphisms to the improvement of biochemical parameters 1 year after Roux-en-Y gastric bypass (RYGB). Methods: Obese patients (n = 150; aged 47.2 ± 10.5 years) were enrolled and weight, body mass index (BMI), and biochemical parameters (glycemia and lipid profile) were evaluated preoperatively and 1 year after RYGB. A GPS was calculated with the polymorphisms rs1801282 of PPARG2, rs4994 of ADRB3, rs1800592 of UCP1, rs659366 and rs669339 of UCP2, rs7121 of GNAS1, and rs5443 of GNB3. We observed that 66.3% of the patients has a GPS >5. Results: During the preoperative period, the GPS showed a significant association with weight (β = -0.163; p = 0.020), BMI (β = -0.169; p = 0.038), and glucose concentrations (β = -0.177; p = 0.036). After sex and age adjustment, a higher GPS was associated with a greater reduction in glycemia (β = -0.158; p = 0.048), triglycerides (β = -0.256; p = 0.002), and total cholesterol (β = -0.172; p = 0.038) concentrations 1 year after surgery. Conclusion: Our data elucidated that a higher GPS provides a greater metabolic benefit of RYGB.

Mammalian target of rapamycin complex 2 signaling in obese women changes after bariatric surgery

OBJECTIVES After bariatric surgery, modifications to signaling pathway networks including those of the metabolic regulator called mammalian or mechanistic target of rapamycin (mTOR) may lead to molecular alterations related to energy source availability, systemic nutrients, and catabolic and anabolic cellular processes. This study aimed to identify gene expression changes with regard to the mTOR complex 2 subunit signaling pathway in obese patients before and after bariatric surgery. METHODS The experimental group included 13 obese women who were examined before (preoperative) and 6 mo after (postoperative) Roux-en-Y gastric bypass (RYGB) surgery. The control group included nine apparently eutrophic women matched by age and without any other metabolic diseases (i.e., no diabetes and no liver or kidney diseases). Peripheral blood mononuclear cell samples were collected for RNA extraction and subsequent microarray analysis. RESULTS After this methodological procedure, we identified 47 000 differentially expressed genes. A subsequent bioinformatic analysis showed that three diferentially expressed genes (rapamycin-insensitive companion of mTOR [RICTOR], phosphoinositide-3-kinase regulatory subunit 1 [PIK3 R1], and hypoxia inducible factor 1 alpha subunit 1A [HIF1 A]) participated in the mTOR signaling pathway. Real-time quantitative polymerase chain reaction revealed that RICTOR, PIK3 R1, and HIF1 A were upregulated 6 mo after RYGB surgery (P <0.05). In addition, patients in the experimental group lost weight significantly and presented significant improvement in biochemical/metabolic variables. CONCLUSIONS The weight loss that was induced by RYGB surgery alters the mTOR signaling pathway and specifically the mTOR complex 2 subunit. The increased expression of genes that act in this pathway such as RICTOR, PIK3 R1, and HIF1 A reflects the induced weight loss and improved metabolic indicators (e.g., insulin resistance and lipolysis) that are evidenced in this study.

Polymorphisms in chronic rhinosinusitis with nasal polyps – a systematic review

INTRODUCTION Chronic rhinosinusitis with nasal polyps is a multifactorial disease with a complex pathophysiology involving multiple genetic and environmental factors. OBJECTIVE The purpose of this work review is to focus on the importance of genetic studies in chronic rhinosinusitis with nasal polyps besides the several barriers that exists for its understanding. METHODS A systematic review on studies of association between single nucleotide polymorphisms and chronic rhinosinusitis with nasal polyps based on a PubMed/Medline and Periódicos CAPES search of all articles published between January 2005 and January 2015 was made. The search was guided on studies containing the terms polymorphisms, rhinosinusitis, and polyps. RESULTS Two studies found an association of MMP-9 and MMP-2 polymorphisms and chronic rhinosinusitis with nasal polyps, but not in patients with recurrent nasal polyps. Other studies found an association of nasal polyps with MMP-9 polymorphisms, but not with MMP-2 ones. There is evidence of an association of LTC4S, NOS2A, PTGDR, MET, COX-2, OSF-2, and LF polymorphisms and the risk of developing nasal polyps, especially when combined with chronic allergic rhinitis and asthma. CONCLUSION Genetic studies on chronic rhinosinusitis with nasal polyps are promising and may offer insights into its pathophysiology, which is likely affected by multiple genetic factors.