In silico analysis of microRNAS targeting the HLA-G 3 ` untranslated region alleles and haplotypes

It has been reported that microRNAs (miRNA) may have allele-specific targeting for the 3` untranslated region (3` UTR) of the HLA-G locus. In a previous study, we reported 11 3`UTR haplotypes encompassing the 14-bp insertion/deletion polymorphism and seven SNPs (+3003 T/C, +3010 C/G, +3027 C/A, +3035 C/T, +3142 C/G, +3187A/G,and +3196 C/G), of which only the +3142 C/G SNP has been reported to influence the binding of miRNAs. Using bioinformatics analyses, we identified putative miRNA-binding sites considering the haplotypes encompassing these eight polymorphic sites, and we ranked the lowest free energies that could potentially lead to an mRNA degradation or translational repression. When a specific haplotype or a particular SNP was associated with a miRNA-binding site, we defined a free energy difference of 4 kcal/mol between alleles to classify them energetically distant. The best results were obtained for the miR-513a-5p, miR-518c*, miR-1262 and miR-92a-1*, miR-92a-2*, miR-661, miR-1224-5p, and miR-433 miRNAs, all influencing one or more of the +3003, +3010, +3027, and +3035 SNPs. The miR-2110, miR-93, miR-508-5p, miR-331-5p, miR-616, miR-513b, and miR-589* miRNAs targeted the 14-bp fragment region, and miR-148a, miR-19a*, miR-152, mir-148b,and miR-218-2 also influenced the +3142C/G polymorphism. These results suggest that these miRNAs might play a relevant role on the HLA-G expression pattern. (C) 2009 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics.

Association study of an epidermal growth factor gene functional polymorphism with the risk and prognosis of gliomas in Brazil

Epidermal growth factor (EGF) plays an important role in cancer. A functional single nucleotide polymorphism (SNP) in the 5`-untranslated region of the EGF gene (+61 A>G) may influence its expression and contribute to cancer predisposition and aggressiveness. Aiming to investigate the role of EGF +61 A>G in the susceptibility to glioma and its prognosis, we performed a case-control study with 165 patients and 200 healthy controls from Brazil. Comparisons of genotype distributions and allele frequencies did not reveal any significant differences between the groups. The mean overall survival was 9.2 months for A/A, 8.2 months for A/G, and 7.7 months for GIG. When survival curves were plotted we found that the +61G allele is associated with poor overall survival (p=0.023) but not with disease-free survival (p=0.527). Our data suggest that, although there is no association between the EGF +61 A>G genotype and glioma susceptibility, this SNP is associated with shorter overall survival of glioma patients in the Brazilian population. Nevertheless, future studies utilizing a larger series are essential for a definitive conclusion. (Int J Biol Markers 2009; 24: 277-81)

WRN Cys1367Arg SNP is not associated with risk and prognosis of gliomas in Southeast Brazil

Werner syndrome (WS) is a premature aging disorder characterized by early onset of symptoms related to normal aging and by a high predisposition to various types of cancer, including gliomas. WS is caused by inherited recessive mutations in the WRN gene, which encodes a helicase considered a caretaker of the genome. Aiming to study the role of WRN Cys1367Arg in glioma susceptibility and oncologic prognosis of patients, we investigated the genotype distribution of this single nucleotide polymorphism in 94 glioma patients and 100 healthy subjects. Comparisons of genotype distributions and allele frequencies did not reveal any significant difference between the groups. Overall and disease-free survival rates were calculated, but no statistically significant difference was observed. Our data suggest that WRN Cys1367Arg SNP is not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.

What is the best equation to estimate the basal energy expenditure of climacteric women?

Objectives The methods currently available for the measurement of energy expenditure in patients, such as indirect calorimetry and double-labelled water, are expensive and are limited in Brazil to research projects. Thus, equations for the prediction of resting metabolic rate appear to be a viable alternative for clinical practice. However, there are no specific equations for the Brazilian population and few studies have been conducted on Brazilian women in the climacteric period using existing and commonly applied equations. On this basis, the objective of the present study was to investigate the concordance between the predictive equations most frequently used and indirect calorimetry for the measurement of resting metabolic rate. Methods We calculated the St. Laurent concordance correlation coefficient between the equations and resting metabolic rate calculated by indirect calorimetry in 46 climacteric women. Results The equation showing the best concordance was that of the FAO/WHO/UNU formula (0.63), which proved to be better than the Harris & Benedict equation (0.55) for the sample studied. Conclusions On the basis of the results of the present study, we conclude that the FAO/WHO/UNU formula can be used to predict better the resting metabolic rate of climacteric women. Further studies using more homogeneous and larger samples are needed to permit the use of the FAO/WHO/UNU formula for this population group with greater accuracy.

Cross-cultural adaptation and reliability of Child-Initiated Pretend Play Assessment (ChIPPA)

Background. Play is an indication of a children`s development. Purpose. Organize a culturally adapt the Child-Initiated Pretend Play Assessment to Brazilian population. Method. Translation and cultural adaptation procedures consisted of translation, synthesis, back translation, author`s approval, and pretest of the assessment. For the pretest, 14 typically developing children were assessed. Was evaluated the use of play materials, duration of the assessment, and reliability. Findings. Play materials and duration of the assessment were appropriate for Brazilian children. Analysis of intra-rater reliability showed good agreement ranging from 0.90 to 1.00. Inter-rater reliability showed good to moderate agreement for five items ranging from 0.76 to 0.59. Four items showed chance to poor agreement (rho = -0.13 to 0.50). Implications. Results of the pretest indicate the Brazilian version of the ChIPPA is potentially useful for Brazilian children. ChIPPA training in Portuguese in Brazil with play observation feedback is recommended to improve inter-rater reliability.

Validation of the National Institutes of Health Stroke Scale, Modified Rankin Scale and Barthel Index in Brazil: The Role of Cultural Adaptation and Structured Interviewing

Background: We aimed to validate three widely used scales in stroke research in a multiethnic Brazilian population. Methods: The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) were translated, culturally adapted and applied by two independent investigators. The mRS was applied with or without a previously validated structured interview. Interobserver agreement (kappa statistics) and intraclass correlation coefficients were calculated. Results: 84 patients underwent mRS (56 with and 28 without a structured interview), 57 BI and 62 NIHSS scoring. Intraclass correlation coefficient was 0.902 for NIHSS and 0.967 for BI. For BI, interobserver agreement was good (kappa = 0.70). For mRS, the structured interview improved interobserver agreement (kappa = 0.34 without a structured interview; 0.75 with a structured interview). Conclusion: The NIHSS, BI and mRS show good validity when translated and culturally adapted. Using a structured interview for the mRS improves interobserver concordance rates. Copyright (C) 2008 S. Karger AG, Basel

Impact of thymidylate synthase promoter and DNA repair gene polymorphisms on susceptibility to childhood acute lymphoblastic leukemia

The aim of this study was to evaluate the frequency of polymorphisms in the TYMS, XRCC1, and ERCC2 DNA repair genes in pediatric patients with acute lymphoblastic leukemia using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) approaches. The study was conducted in 206 patients and 364 controls from a Brazilian population. No significant differences were observed among the analyzed groups regarding XRCC1 codon 399 and codon 194 and ERCC2 codon 751 and codon 312 polymorphisms. The TYMS 3R variant allele was significantly associated with a reduced risk of childhood ALL, represented by the sum of heterozygous and polymorphic homozygous genotypes (odds ratio 0.60; 95% confidence interval 0.37-0.99). The results suggest that polymorphism in TYMS may play a protective role against the development of childhood ALL.

The genetic structure of 3 ` untranslated region of the HLA-G gene: polymorphisms and haplotypes

The HLA-G gene is predominantly expressed at the maternal-fetal interface. It has been associated with maternal-fetal tolerance and in the inhibition of cytotoxic T lymphocyte and natural killer cytolytic functions. At least two variations in the 3` untranslated region (UTR) of HLA-G locus are associated with HLA-G expression levels, the 14-bp deletion/insertion polymorphism and the +3142 single-nucleotide polymorphism (SNP). However, this region has not been completely characterized yet. The variability of the 3`UTR of HLA-G gene and its haplotype structure were characterized in 155 individuals from Brazil, as well as HLA-G alleles associated with each of the 3`UTR haplotype. The following eight variation sites were detected: the 14-bp polymorphism and SNPs at the positions +3003T/C, +3010C/G, +3027A/C, +3035C/T, +3142G/C, +3187A/G and +3196C/G. Similarly, 11 different 3`UTR haplotypes were identified and several HLA-G alleles presented only one 3`UTR haplotype. In addition, a high linkage disequilibrium among the variation sites was detected, especially among the 14-bp insertion and the alleles +3142G and +3187A, all previously associated with low mRNA availability, demonstrating that their effects are not independent. The detailed analyses of 3`UTR of the HLA-G locus may shed some light into mechanisms underlying the regulation of HLA-G expression. Genes and Immunity (2010) 11, 134-141; doi: 10.1038/gene.2009.74; published online 1 October 2009

Oral manifestations of human T-cell lymphotropic virus infection in adult patients from Brazil

Objective: Human T-cell lymphotropic virus type 1 (HTLV-1) was the first human retrovirus discovered and its pathogenesis is related to T cells infection. This study aimed to verify the presence of oral manifestations in a Brazilian population of patients who was seropositive for HTLV, and identify risk factors for oral manifestations. Subjects and methods: An assessment was made of 139 patients at the Emilio Ribas Institute of Infectious Diseases. Results: A total of 112 (80.5%) patients were HTLV-1, 26 (18.7%) were HTLV-2+. About 35.2% of patients had myelopathy/tropical spastic paraparesis (HAM/TSP), with 48 of them being HTLV-1+ and one patient was seropositive for HTLV-1 and -2. The most common oral manifestations were: xerostomia (26.8%), candidiasis (20.8%), fissured tongue (17.9%), and loss of tongue papillae (10.0%). A multivariate logistic regression analysis showed that HAM/TSP is an independent risk factor for xerostomia (P = 0.02). The patients who were HAM/TSP+ were three times more likely to develop xerostomia when compared with patients without HAM/TSP (odds ratio = 2.69, 95% confidence interval = 1.17-6.17). Conclusion: Despite the fact that the findings of this study suggest a relationship between xerostomia and HAM/TSP, more studies should be developed to show what the association would be between xerostomia presented by HTLV patients and pathogenesis of the virus.

Trends in systemic lupus erythematosus mortality rates in the state of Sao Paulo, Brazil from 1985 to 2004

Objectives To estimate mortality rates and mortality trends from SLE in the state of Sao Paulo, Brazil. Material and methods The official data bank was used to study all deaths occurred from 1985 to 2004 in which SLE was mentioned as the underlying cause of death. Besides the overall mortality rate, the annual gender- and age-specific mortality rates were estimated for each calendar year by age bracket (0-19 years, 20-39 years, 40-59 years and over 60 years) and for the sub-periods 1985-1995 (first) and 1996-2004 (second), by decades. Chi-square test was used to compare the mortality rates between the two periods, as well the mortality rates according to educational level considering years of study. Pearson correlation coefficient test was used to analyse mortality trends. The crude rates were adjusted for age by the direct method, using the standard Brazilian population in 2000. Results A total of 2,601 deaths (90% female) attributed to SLE were analysed. The mean age at death was significantly higher in the second than in the first sub-period (36.6 +/- 15.6 years vs. 33.9 +/- 14.0 years; p<0.001). The overall adjusted mortality rate was 3.8 deaths/million habitants/year for the entire period and 3.4 deaths/million inhabitants/year for the first and 4.0 deaths/million inhabitants/year for the second sub-period (p<0.001). In each calendar year, the mortality rate was significantly lower for the better educated group. Throughout the period, there was a significant increase in mortality rates only among women over 40. Conclusion SLE patients living in the state of Silo Paulo still die at younger ages than those living in developed countries. Our data do not support the theory that there was an improvement in the SLE mortality rate in the last 20 years in the state of Sao Paulo. Socio-economic factors, such as the difficulty to get medical care and adequate treatment, may be the main factors to explain the worst prognosis for our patients.

Association of genetic variants in the adiponectin encoding gene (ADIPOQ) with type 2 diabetes in Japanese Brazilians

Aim: The objective of this study is to assess the contribution of ADIPOQ variants to type 2 diabetes in Japanese Brazilians. Methods: We genotyped 200 patients with diabetes mellitus (100 male and 100 female, aged 55.0 years [47.5-64.0 years]) and 200 control subjects with normal glucose tolerant (NGT) (72 male and 128 female, aged 52.0 years [43.5-64.5 years]). Results: Whereas each polymorphism studied (T45G, G276T, and A349G) was not significantly associated with type 2 diabetes mellitus, the haplotype GGA was overrepresented in our diabetic population (9.3% against 3.1% in NGT individuals, P=.0003). Also, this haplotype was associated with decreased levels of adiponectin. We also identified three mutations in exon 3: I164T, R221S, and H241P, but, owing to the low frequencies of them, associations with type 2 diabetes could not be evaluated. The subjects carrying the R221S mutation had plasma adiponectin levels lower than those without the mutation (2.10 mu g/ml [1.35-2.55 mu g/ml] vs. 6.68 mu g/ml [3.90-11.23 mu g/ml], P=.015). Similarly, the I164T mutation carriers had mean plasma adiponectin levels lower than those noncarriers (3.73 mu g/ml [3.10-4.35 mu g/ml] vs. 6.68 mu g/ml [3.90-11.23 mu g/ml]), but this difference was not significant (P=.17). Conclusions: We identified in the ADIPOQ gene a risk haplotype for type 2 diabetes in the Japanese Brazilian population. (C) 2010 Elsevier Inc. All rights reserved.

Novel mutation in the adiponectin (ADIPOQ) gene is associated with hypoadiponectinaemia in Japanese-Brazilians

P>Objective Adiponectin is an important mediator of insulin sensitivity, encoded by the ADIPOQ gene. Here we describe two Japanese-Brazilian families with hypoadiponectinaemia due to a novel mutation in ADIPOQ. Design and patients In this study, we examined the entire translated regions of adiponectin in Japanese-Brazilians, a population with one of the highest prevalence rates of diabetes worldwide. We screened 200 patients with type 2 diabetes (DM) and 240 age-matched subjects with normal glucose tolerance. Results A novel heterozygous T deletion at position 186 in exon 2 of ADIPOQ, causing a frameshift at codon 62 and leading to a premature termination at codon 168 (p.Gly63ValfsX106), was found in two individuals with diabetes. This mutation was not found in 240 nondiabetic control subjects. In addition, we screened the mutation in an expanded set of 100 nondiabetic subjects from the general Brazilian population, but we found no mutations. In addition, six family members of the probands were identified as mutation-carriers. Individuals who were mutation-carriers had markedly low plasma adiponectin concentrations compared with those without the mutation [DM: 0 center dot 65 (0 center dot 59-1 center dot 34) mu g/ml vs. 5 center dot 30 (3 center dot 10-8 center dot 55) mu g/ml, P < 0 center dot 0001; normal glucose tolerance: 0 center dot 95 (0 center dot 76-1 center dot 48) mu g/ml vs. 8 center dot 50 (5 center dot 52-14 center dot 55) mu g/ml, P = 0 center dot 003]. All individuals carrying the p.Gly63ValfsX106 mutation and older than 30 years were found to be diabetic. Conclusions We describe for the first time a frameshift mutation in exon 2 of the ADIPOQ gene, which modulates adiponectin levels and may contribute to the genetic risk of late-onset diabetes in Japanese-Brazilians.

Nutritional information of meals supplied by companies, participating in the workers` meal program in Sao Paulo, Brazil

Objective. To compare the nutritional value of meals provided by companies participating in the Workers` Meal Program in the city of Sao Paulo, Brazil, to the nutritional recommendations and guidelines established by the Ministry of Health for the Brazilian population. Methods. The 72 companies studied were grouped according to economic sector (industrial, services, or commerce), size (micro, small, medium, or large), meal preparation modality (prepared on-site by the company itself, on-site by a hired caterer, or off-site by a hired caterer), and supervision by a dietitian (yes or no). The per capita amount of food was determined based on the lunch, dinner, and supper menus for three days. The nutritional value of the meals was defined by the amount of calories, carbohydrates, protein, total fat, polyunsaturated fat, saturated fat, trans fat, sugars, cholesterol, and fruits and vegetables. Results. Most of the menus were deficient in the number of fruits and vegetables (63.9%) and amount of polyunsaturated fat (83.3%), but high in total fat (47.2%) and cholesterol (62.5%). Group 2, composed of mostly medium and large companies, supervised by a dietician, belonging to the industrial and/or service sectors, and using a hired caterer, on averaged served meals with higher calorie content (P < 0.001), higher percentage of polyunsaturated fat (P < 0.001), more cholesterol (P = 0.015), and more fruits and vegetables (P < 0.001) than Group 1, which was composed of micro and small companies from the commercial sector, that prepare the meals themselves on-site, and are not supervised by a dietitian. Regarding the nutrition guidelines set for the Brazilian population, Group 2 meals were better in terms of fruit and vegetable servings (P < 0.001). Group I meals were better in terms of cholesterol content (P = 0.05). Conclusions. More specific action is required targeting company officers and managers in charge of food and nutrition services, especially in companies without dietitian supervision.

Physical analyses of compost from composting plants in Brazil

Nowadays the composting process has shown itself to be an alternative in the treatment of municipal solid wastes by composting plants. However, although more than 50% of the waste generated by the Brazilian population is composed of matter susceptible to organic composting, this process is, still today, insufficiently developed in Brazil, due to low compost quality and lack of investments in the sector. The objective of this work was to use physical analyses to evaluate the quality of the compost produced at 14 operative composting plants in the Sao Paulo State in Brazil. For this purpose, size distribution and total inert content tests were done. The results were analyzed by grouping the plants according to their productive processes: plants with a rotating drum, plants with shredders or mills, and plants without treatment after the sorting conveyor belt. Compost quality was analyzed considering the limits imposed by the Brazilian Legislation and the European standards for inert contents. The size distribution tests showed the influence of the machinery after the sorting conveyer on the granule sizes as well as the inert content, which contributes to the presence of materials that reduce the quality of the final product. (C) 2007 Elsevier Ltd. All rights reserved.

Influence of SCARB1 polymorphisms on serum lipids of hypercholesterolemic individuals treated with atorvastatin

Background: The SR-BI is a key component on the cholesterol metabolism. Polymorphisms in the SR-BI gene (SCARB1) were related with variations on plasma lipoprotein profile and other risk factors for cardiovascular disease. We tested the relationship of 3 SCARB1 single nucleotide polymorphisms (SNPs) with hypercholesterolemia in a Brazilian population and whether these variants can influence lipid-lowering response to atorvastatin. Methods: c.4G>A, c.726+54C>T and c.1050C>T SNPs and serum concentrations of lipid and apolipoproteins were evaluated in 147 hypercholesterolemic (HC) and 185 normolipidemic (NL) unrelated Brazilian subjects. HC patients were treated with atorvastatin (10 mg/day/4 weeks). Results: Frequencies of SCARB1 polymorphisms were similar between the HC and NL groups (p>0.05). The T allele for c.726+54C>T was associated with higher LDL-c in NL and with higher apoB and apoB/apoAI in HC (p<0.05). HC individuals carrying c.1050C allele carriers (CC and CT genotypes) had lower change of total cholesterol, LDL-c, apoB and apoB/apoAI ratio (p<0.05) than the TT genotype carriers in response to atorvastatin. Conclusion: The SCARB1 polymorphisms are related with variations in serum lipids in the Brazilian population and c.1050C>T SNP is associated with lipid-lowering atorvastatin response. (C) 2010 Elsevier B.V. All rights reserved.