Risk factors across the life course and dementia in a Brazilian population: results from the Sao Paulo Ageing & Health Study (SPAH)

Background Several mechanisms have been suggested to explain the association between adversities across life and dementia. This study aimed to investigate the association between indicators of socioeconomic disadvantages throughout the life-course and dementia among older adults in Sao Paulo, Brazil and to explore possible causal pathways. Methods We used baseline data from the SPAH study which involved participants aged 65 years and older (n = 2005). The outcome of interest was prevalent dementia. Exposures included in the analyses were socioeconomic position (SEP) indicators in childhood (place of birth and literacy) and adulthood (occupation and income), anthropometric measurements as markers of intrauterine and childhood environment (head circumference and leg length), smoking, diabetes and hypertension. Logistic regression models were used to test the hypothesized pathways and to assess whether there was an association between cumulative adversities across the life course and prevalent dementia. Results Indicators of socioeconomic disadvantage in early life were associated with increased prevalence of dementia. This association was partially mediated through adulthood SEP. Head circumference and leg length were also clearly associated with dementia but there was no evidence that this association was mediated by early life socioeconomic disadvantage. There was an association between cumulative unfavourable conditions across the life course and dementia. Conclusions Early life disadvantages seem to operate through biological mechanisms associated with passive brain reserve and opportunities in life representing active cognitive reserve. Prevention of dementia should start early in life and continue through life span as seen with many other chronic diseases.

DC-SIGN (CD209) gene promoter polymorphisms in a Brazilian population and their association with human T-cell lymphotropic virus type 1 infection

This study evaluated four polymorphisms located in the DC-SIGN (CD209) gene promoter region (positions -336, -332 -201 and -139) in DNA samples from four Brazilian ethnic groups (Caucasians, Afro-Brazilian, Asians and Amerindians) to establish the population distribution of these single-nucleotide polymorphisms (SNPs) and correlated DC-SIGN polymorphisms and infection in samples from human T-cell lymphotropic virus type 1 (HTLV-1)-infected individuals. To identify CD209 SNPs, 452 bp of the CD209 promoter region were sequenced and the genotype and allelic frequencies were evaluated. This is the first study to show genetic polymorphism in the CD209 gene in distinct Brazilian ethnic groups with the distribution of allelic and genotypic frequency. The results showed that -336A and -139A SNPs were quite common in Asians and that the -201T allele was not observed in Caucasians, Asians or Amerindians. No significant differences were observed between individuals with HTLV-1 disease and asymptomatic patients. However, the -336A variant was more frequent in HTLV-1 -infected patients [HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), 80%; healthy asymptomatic HTLV-1 carriers, 90 %] than in the control group (70 %) [P=0.0197, odds ratio (OR)=2.511, 95 % confidence interval (CI)=1.218-5.179). In addition, the -139A allele was found to be associated with protection against HTLV-1 infection (P=0.0037, OR=0.3758, 95% CI=0.1954-0.7229) when the HTLV-1 -infected patients as a whole were compared with the healthy-control group. These observations suggest that the -139A allele may be associated with HTLV-1 infection, although no significant association was observed among asymptomatic and HAM/TSP patients. In conclusion, the variation observed in SNPs -336 and -139 indicates that this lectin may be of crucial importance in the susceptibility/transmission of HTLV-1 infections.

HLA-G polymorphism and transitional cell carcinoma of the bladder in a Brazilian population

The morphologic appearance and clinical behavior of the human urinary bladder papillary transitional cell carcinoma (TCC) probably result from a complex interaction between carcinogenic insults and host resistance during the patient`s life. While the main recognized risk factors are of environmental origin (e.g. smoking), relatively little information exists about the susceptibility to TCC development. The human leukocyte antigen G (HLA-G) molecule plays an important role in immune response regulation and has been implicated in the inhibition of the cytolytic function of natural killer and cytotoxic T cells. Several lines of evidence indicate that HLA-G polymorphisms influence the expression level and production of different HLA-G isoforms. The aim of this study was to explore a possible influence of the HLA-G polymorphism on the susceptibility to urinary bladder TCC development and progression in smokers and nonsmokers Brazilian subjects. The HLA-G locus was found to be associated with susceptibility to TCC development and progression. The G*0104 allelic group (specially the G*010404 allele) and the G*0103 allele were associated with a tobacco-dependent influence on TCC development. The G*0104 group was associated with progression to high-grade tumors, irrespective of smoking habit, while the G*0103 allele was associated to high-grade tumor only in smoking patients. Our results are an evidence that the HLA-G locus itself, or as part of an extended haplotype encompassing this chromosome region (particularly the HLA-A given the high linkage disequilibrium observed between them in this data series), may be associated with TCC susceptibility and tumor progression, suggesting a tobacco-dependent influence of these polymorphisms.

Estimates of Interethnic Admixture in the Brazilian Population Using a Panel of 24 X-Linked Insertion/Deletion Markers

Objectives. In this study, we aimed to identify ancestry informative haplotypes and make interethnic admixture estimates using X-chromosome markers. Methods. A significant sample (461 individuals) of European, African, and Native American populations was analyzed, and four linkage groups were identified. The data obtained were used to describe the ancestral contribution of populations from four different geographical regions of Brazil (745 individuals). Results. The global interethnic admixture estimates of the four mixed populations under investigation were calculated applying all the 24 insertion/deletion (INDEL) markers. In the North region, a larger Native Americans ancestry was observed (42%). The Northeast and Southeast regions had smaller Native American contribution (27% in both of them). In the South region, there was a large European contribution (46%). Conclusions. The estimates obtained are compatible with expectations for a colonization model with biased admixture between European men (one X chromosome) and Native American and African women (two X chromosomes), so the 24 X-INDEL panel described here can be a useful to make admixture interethnic estimates in Brazilian populations. Am. J. Hum. Biol. 22:849-852,2010. (C) 2010 Wiley-Liss, Inc.

Detection of Spinal Muscular Atrophy Carriers in a Sample of the Brazilian Population

Background: Spinal muscular atrophy is a common autosomal recessive neuromuscular disorder caused by mutations in the SMN1 gene. Identification of spinal muscular atrophy carriers has important implications for individuals with a family history of the disorder and for genetic counseling. The aim of this study was to determine the frequency of carriers in a sample of the nonconsanguineous Brazilian population by denaturing high-performance liquid chromatography (DHPLC). Methods: To validate the method, we initially determined the relative quantification of DHPLC in 28 affected patients (DHPLC values: 0.00) and 65 parents (DHPLC values: 0.49-0.69). Following quantification, we studied 150 unrelated nonconsanguineous healthy individuals from the general population. Results: Four of the 150 healthy individuals tested (with no family history of a neuromuscular disorder) presented a DHPLC value in the range of heterozygous carriers (0.6-0.68). Conclusions: Based on these results, we estimated there is a carrier frequency of 2.7% in the nonconsanguineous Brazilian population, which is very similar to other areas of the world where consanguineous marriage is not common. This should be considered in the process of genetic counseling and risk calculations. Copyright (C) 2011 S. Karger AG, Basel

Polymorphisms in genes encoding drugs and xenobiotic metabolizing enzymes in a Brazilian population

Polymorphic variations of several genes associated with drugs and xenobiotic metabolism have been linked to the factors that predispose to the carcinogenesis process. As considerable interindividual and interethnic variation in metabolizing enzyme activity has been associated with polymorphic alleles, we evaluated the frequency of the polymorphisms of CYP2D6, EPHX1 and NQO1 genes in 361 Brazilian individuals separated by ethnicity (European and African ancestry), using the polymerase chain reaction-restriction fragment length (PCR-RFLP) method. The allele frequencies of the variants *3 and *4 for the gene CYP2D6 were 0.04 and 0.14 for white subjects and 0.03 and 0.10 for black individuals, respectively. For the both variants of the gene EPHX1, we found higher allele frequencies among white individuals compared with mulatto subjects (0.62 vs 0.54 and 0.18 vs 0.14, respectively); however, these differences were not statistically significant (p = 0.39 and 0.56, respectively). For the NQO1 gene we observed a higher frequency of the homozygous genotype among black individuals (7.9%) compared with white subjects (6.3%) (p = 0.003). The genotype frequencies were within the Hardy-Weinberg equilibrium. We concluded that the allele frequencies of CYP2D6, EPHX1 and NQO1 gene polymorphisms in this Brazilian population showed ethnic variability when compared with those observed in other populations.

Systemic lupus erythematosus: Association with KIR and SLC11A1 polymorphisms, ethnic predisposition and influence in clinical manifestations at onset revealed by ancestry genetic markers in an urban Brazilian population

Systemic lupus erythematosus (SLE) is an autoimmune disorder of the connective tissue with a wide and heterogeneous spectrum of manifestations, with renal and neurological involvement usually related to worse prognosis. SLE more frequently affects females of reproductive age, and a high prevalence and renal manifestation seem to be associated with non-European ethnicity. The present study aims to investigate candidate loci to SLE predisposition and evaluate the influence of ethnic ancestry in the disease risk and clinical phenotypic heterogeneity of lupus at onset. Samples represented by 111 patients and 345 controls, originated from the city of Belem, located in the Northern Region of Brazil, were investigated for polymorphisms in HLA-G, HLA-C, SLC11A1, MTHFR, CASP8 and 15 KIR genes, in addition to 89 Amerindian samples genotyped for SLC11A1. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. Predisposition to SLE was associated with GTGT deletion at the SLC11A1 3`UTR, presence of KIR2DS2 +/KIR2DS5 +/KIR3DS1 + profile, increased number of stimulatory KIR genes, and European and Amerindian ancestries. The ancestry analysis ruled out ethnic differences between controls and patients as the source of the observed associations. Moreover, the African ancestry was associated with renal manifestations. Lupus (2011) 20, 265-273.

Analysis of five polymorphic DNA markers for indirect genetic diagnosis of haemophilia A in the Brazilian population

Hemophilia A is an X-linked, inherited, bleeding disorder caused by the partial or total inactivity of the coagulation factor VIII (FVIII). Due to difficulties in the direct recognition of the disease-associated mutation in the F8 gene, indirect diagnosis using polymorphic markers located inside or close to the gene is used as an alternative for determining the segregation of the mutant gene within families and thus for detecting carrier individuals and/or assisting in prenatal diagnosis. This study characterizes the allelic and haplotype frequencies, genetic diversity, population differentiation and linkage disequilibrium of five microsatellites (F8Int1, F8Int13, F8Int22, F8Int25.3 and IKBKG) in samples of healthy individuals from Sao Paulo, Rio Grande do Sul and Pernambuco and of patients from Sao Paulo with haemophilia A to determine the degree of informativeness of these microsatellites for diagnostic purposes. The interpopulational diversity parameters highlight the differences among the analyzed population samples. Regional differences in allelic frequencies must be taken into account when conducting indirect diagnosis of haemophilia A. With the exception of IKBKG, all of the microsatellites presented high heterozygosity levels. Using the markers described, diagnosis was possible in 10 of 11 families. The F8Int22, F8Int1, F8Int13, F8Int25.3 and IKBKG microsatellites were informative in seven, six, five and two of the cases, respectively, demonstrating the effectiveness of using these microsatellites in prenatal diagnosis and in carrier identification in the Brazilian population.

Performance of a Brazilian population on the test of functional health literacy in adults

OBJECTIVE: To analyze the scoring obtained by an instrument, which evaluates the ability to read and understand items in the health care setting, according to education and age. METHODS: The short version of the Test of Functional Health Literacy in Adults was administered to 312 healthy participants of different ages and years of schooling. The study was conducted between 2006 and 2007, in the city of São Paulo, Southeastern Brazil. The test includes actual materials such as pill bottles and appointment slips and measures reading comprehension, assessing the ability to read and correctly pronounce a list of words and understand both prose passages and numerical information. Pearson partial correlations and a multiple regression model were used to verify the association between its scores and education and age. RESULTS: The mean age of the sample was 47.3 years(sd=16.8) and the mean education was 9.7 years(sd=5; range: 1 - 17). A total of 32.4% of the sample showed literacy/numeracy deficits, scoring in the inadequate and marginal functional health literacy ranges. Among the elderly (65 years or older) this rate increased to 51.6%. There was a positive correlation between schooling and scores (r=0.74; p<0.01) and a negative correlation between age and the scores (r=-0.259; p<0.01). The correlation between the scores and age was not significant when the effects of education were held constant (rp=-0.031, p=0.584). A significant association (B=3.877, Beta =0.733; p<0.001) was found between schooling and scores. Age was not a significant predictor in this model (B=-0.035, Beta=-0.22; p=0.584). CONCLUSIONS: The short version of the Test of Functional Health Literacy in Adults was a suitable tool to assess health literacy in the study population. The high number of individuals classified as functional illiterates in this test highlights the importance of special assistance to help them properly understand directions for healthcare.

TESTING A SUBTYPE-SPECIFIC GP41 AMPLIFICATION METHOD FOR GENOTYPING INDIVIDUALS INFECTED BY HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 IN THE BRAZILIAN POPULATION OF ITAJAÍ, SOUTH BRAZIL

The method used by YAGYU et al. for the subtype-specific polymerase chain reaction (PCR) amplification of the gp41 transmembrane region of the human immunodeficiency virus type-1 (HIV-1) env gene, was tested. HIV-1 proviral DNA from 100 infected individuals in Itajaí, South Brazil was used to analyze this method. Seventy individuals were determined according to this method as having PCR products at the expected size for subtypes B, C, D and F. Of these individuals, 26 (37.1%) were observed as having the expected amplification for subtype C, and 42 (60%) were observed as having the expected products for subtypes B and D. Of the subtype B and D amplicons, 16 (22.9%) were classified as subtype D, and 26 (37.1%) were classified as subtype B. Two individuals (2.9%) had amplicons that were observed after subtype F-specific amplification was performed. Sequencing and comparing the patient sequences to reference sequences confirmed the classification of sequences of subtypes C and B. However, sequences that were falsely determined as being D and F in the PCR assay were determined as being subtypes C and B, respectively, by sequence analysis. For those individuals from whom no amplified products were obtained, a low viral load that was indicated in their patient history may explain the difficulty in subtyping by PCR methods. This issue was demonstrated by the results of ANOVA when testing the effect of viral load on the success of PCR amplification. The alignment of the obtained sequences with HIV-1 reference sequences demonstrated that there is high intra-subtype diversity. This indicates that the subtype-specific primer binding sites were not conserved or representative of the subtypes that are observed in the Brazilian populations, and that they did not allow the correct classification of HIV-1 subtypes. Therefore, the proposed method by YAGYU et al. is not applicable for the classification of Brazilian HIV-1 subtypes.

Salivary gland tumors in a Brazilian population: a retrospective study of 124 cases

Salivary gland tumors constitute a highly heterogeneous histopathologic group. There are few epidemiological studies of large series of benign and malignant salivary gland tumors in Brazil. MATERIAL AND METHODS: Hospital records of 124 patients with salivary gland tumors diagnosed from January 1993 to December 1999 were reviewed. The patients were analyzed according to gender, age, size, location, and histopathology of the tumor. RESULTS AND CONCLUSIONS: Patients with benign and malignant tumors presented with a mean age of 47.7 and 48.8 years, respectively. The frequency of benign tumors was 80% (n = 99) and malignant tumors 20% (n = 25). Tumors were localized in the parotid gland 71% (n = 88), in the submandibular gland 24% (n = 30), and in the minor salivary glands 5% (n = 6). The most common benign tumors were pleomorphic adenoma in 84% (n = 84) and Warthin's tumor in 13% (n = 13). Among malignant tumors, mucoepidermoid carcinoma was the most common in 52% (n = 13), adenoid cystic carcinoma occurred in 20% (n = 5), and carcinoma ex pleomorphic adenoma was detected in 12% (n = 3).

Systemic hypertension, diabetes mellitus, and dyslipidemia in relation to body mass index: evaluation of a Brazilian population

OBJECTIVE: To determine the prevalence of systemic hypertension, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia in a Brazilian population in relation to body mass index. METHOD: Retrospective evaluation of 1213 adults (mean age: 45.2 ± 12.8; 80.6% females) divided into groups according to body mass index [normal (18.5 - 24.4 kg/m²); overweight (25 - 29.9 kg/m²); grade 1 obesity (30 - 34.9 kg/m²); grade 2 obesity (35 - 39.9 kg/m²), and grade 3 obesity (> 40 kg/m²)]. The prevalence of hypertension, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia were analyzed in each group. The severity of cardiovascular risk was determined. High-risk patients were considered those reporting 2 or more of the following factors: systemic hypertension, HDL < 35 mg/dL, total cholesterol > 240 mg/dL, triglycerides > 200 mg/dL when HDL < 35 mg/dL, and glycemia > 126 mg/dL. Moderate-risk patients were those reporting 2 or more of the following factors: systemic hypertension, HDL < 45, triglycerides > 200 mg/dL, and total cholesterol > 200 mg/dL. RESULTS: The prevalence of systemic hypertension, diabetes mellitus, hypertriglyceridemia, and low HDL-cholesterol levels increased along with weight, but the prevalence of hypercholesterolemia did not. The odds ratio adjusted for gender and age, according to grade of obesity compared with patients with normal weight were respectively 5.9, 8.6, and 14.8 for systemic hypertension, 3.8, 5.8, and 9.2 for diabetes mellitus and 1.2, 1.3, and 2.6 for hypertriglyceridemia. We also verified that body mass index was positively related to cardiovascular high risk (P < .001) CONCLUSION: In our population, cardiovascular risk increased along with body mass index.

An Equation for the Prediction of Oxygen Consumption in a Brazilian Population

Background: The equations predicting maximal oxygen uptake (VO2max or peak) presently in use in cardiopulmonary exercise testing (CPET) softwares in Brazil have not been adequately validated. These equations are very important for the diagnostic capacity of this method. Objective: Build and validate a Brazilian Equation (BE) for prediction of VO2peak in comparison to the equation cited by Jones (JE) and the Wasserman algorithm (WA). Methods: Treadmill evaluation was performed on 3119 individuals with CPET (breath by breath). The construction group (CG) of the equation consisted of 2495 healthy participants. The other 624 individuals were allocated to the external validation group (EVG). At the BE (derived from a multivariate regression model), age, gender, body mass index (BMI) and physical activity level were considered. The same equation was also tested in the EVG. Dispersion graphs and Bland-Altman analyses were built. Results: In the CG, the mean age was 42.6 years, 51.5% were male, the average BMI was 27.2, and the physical activity distribution level was: 51.3% sedentary, 44.4% active and 4.3% athletes. An optimal correlation between the BE and the CPET measured VO2peak was observed (0.807). On the other hand, difference came up between the average VO2peak expected by the JE and WA and the CPET measured VO2peak, as well as the one gotten from the BE (p = 0.001). Conclusion: BE presents VO2peak values close to those directly measured by CPET, while Jones and Wasserman differ significantly from the real VO2peak.

p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample

Background:Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL).Objective:To investigate the relationships between p.Q192R SNP ofPON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample.Methods:We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317).Results:The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) μmol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/dL; p < 0.001) and apo A-I (RR = 140.76 ± 36.39; RQ = 147.62 ± 36.92; QQ = 147.49 ± 36.65 mg/dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques.Conclusion:In low-risk individuals, the presence of the p.192Q variant ofPON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis.

Mitotic and meiotic chromosomes of a southern Brazilian population of Boophilus microplus (Acari, Ixodidae)

Using conventional staining with acetic orcein and C-banding techniques it was investigated constitutive heterochromatin chromosomal polymorphisms and the mitotic and the meiotic behavior of male and female chromosomes of Boophilus microplus (Canestrini, 1887). Some differences were detected in the population of southern Brazil as compared to the data of other authors for populations in other latitudes. The differences being mainly concerned with the distribution of constitutive centromeric heterochromatin and variation in the length of heterochromatic blocks in the pericentromeric regions of some chromosome pairs.