Frequency and clinical profile of patients with polycystic kidney disease in Southern Brazil

Background. Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic nephropathies, affecting one in every 800-1000 individuals in the worldwide general population and 5-10% of hemodialysis patients. Little data concerning the prevalence of ADPKD in Brazil are available. Thus, the aim of the present study was to investigate both the frequency and clinical profile of ADPKD among hemodialysis patients in south of Brazil. Methods. This cross-sectional study consisted of patients from 24 hemodialysis centers. Patients were screened for ADPKD by clinical, laboratorial, and image examination in medical records. Results. Of 1326 patients on hemodialysis in the south of Brazil that composed this study, 99 (7.5%) had polycystic kidney as primary cause for chronic renal failure. Comparisons between ADPKD and non-ADPKD patients revealed no differences regarding mean age, gender, and ethnicity. Conclusions. Our data revealed that ADPKD is prevalent among patients on hemodialysis in the south of Brazil. In addition, the clinical profile of ADPKD is similar to reported data from North America and Europe, putatively due to the similar ethnic composition mainly based on European descents.

Rhipicephalus (Boophilus) microplus: Distinct acute phase proteins vary during infestations according to the genetic composition of the bovine hosts, Bos taurus and Bos indicus

Tick bites may trigger acute phase responses. Positive and negative acute phase proteins were measured in infested cattle genetically resistant and susceptible to ticks. During heavier infestations levels of haptoglobin increased significantly in susceptible bovines; levels of serum amyloid A increased in resistant bovines; levels of alpha-l-acid glycoprotein decreased significantly in resistant bovines; levels of transferrin decreased significantly in susceptible bovines. In conclusion, tick infestations trigger acute phase responses and enhancement of specific acute phase proteins differs according to the genetic composition of hosts. Acute phase proteins may constitute useful biological signatures for monitoring the stress induced by tick infestations. (c) 2007 Elsevier Inc. All rights reserved.

Effect of angiotensin converting enzyme inhibitor enalapril on body weight and composition in young rats

Obesity is considered a worldwide public health problem showing an increased prevalence in developing countries, with urgent need for new and more efficient drugs and therapies. Enalapril, an angiotensin-I converting enzyme inhibitor (ACEi), is classically used in antihypertensive therapies, however, earlier publications have shown that this drug could also have significant impact on body weight in rats as well as in humans, besides reducing blood pressure. The effect of this drug in the white adipose tissue has been neglected for long time, even considering that most components of the renin-angiotensin and kallikrein-kinin system are expressed in this tissue. Furthermore, the adipose tissue is considered today as one of the most important sites for endocrine/inflammatory regulation of appetite and energy output and AngII has been linked to the metabolism in this tissue. Therefore, we analyzed the influence of chronic enalapril treatment in normotensive rats at earlier ages, evaluating body weight, energy homeostasis, lipid profile and serum levels of the hormones leptin and insulin, in the presence of a standard or a palatable hyperlipidic diet regimen for one month. Our results show that enalapril treatment is able to reduce body fat on both diets, without alteration in serum lipid profile. Furthermore, animals receiving enalapril showed reduction in food intake, leptin level and energy intake. In summary, these findings show for the first time that the ACEi enalapril reduces body fat in young normotensive rats and highlights a novel target to treat obesity and associated diseases. (c) 2007 Elsevier B.V. All rights reserved.

PREDICTION OF FAT-FREE MASS BY BIOELECTRICAL IMPEDANCE ANALYSIS IN OLDER ADULTS FROM DEVELOPING COUNTRIES: A CROSS-VALIDATION STUDY USING THE DEUTERIUM DILUTION METHOD

Objective: Several limitations of published bioelectrical impedance analysis (BIA) equations have been reported. The aims were to develop in a multiethnic, elderly population a new prediction equation and cross-validate it along with some published BIA equations for estimating fat-free mass using deuterium oxide dilution as the reference method. Design and setting: Cross-sectional study of elderly from five developing countries. Methods: Total body water (TBW) measured by deuterium dilution was used to determine fat-free mass (FFM) in 383 subjects. Anthropometric and BIA variables were also measured. Only 377 subjects were included for the analysis, randomly divided into development and cross-validation groups after stratified by gender. Stepwise model selection was used to generate the model and Bland Altman analysis was used to test agreement. Results: FFM = 2.95 - 3.89 (Gender) + 0.514 (Ht(2)/Z) + 0.090 (Waist) + 0.156 (Body weight). The model fit parameters were an R(2), total F-Ratio, and the SEE of 0.88, 314.3, and 3.3, respectively. None of the published BIA equations met the criteria for agreement. The new BIA equation underestimated FFM by just 0.3 kg in the cross-validation sample. The mean of the difference between FFM by TBW and the new BIA equation were not significantly different; 95% of the differences were between the limits of agreement of -6.3 to 6.9 kg of FFM. There was no significant association between the mean of the differences and their averages (r = 0.008 and p = 0.2). Conclusions: This new BIA equation offers a valid option compared with some of the current published BIA equations to estimate FFM in elderly subjects from five developing countries.

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.

Comparison of bioelectrical impedance with skinfold thickness and x-ray absorptiometry to measure body composition in HIV-infected with lipodistrophy

Introduction: Human immunodeficiency virus (HIV)associated lipodystrophy syndrome (LS) includes body composition and metabolic alterations. Lack of validated criteria and tools make difficult to evaluate body composition in this group. Objective: The aim of the study was to compare different methods to evaluate body composition between Brazilians HIV subjects with (HIV+LIPO+) or without LS (HIV+LIPO-) and healthy subjects (Control). Methods: in a cross-sectional analyses, body composition was measured by bioelectrical impedance analysis (BIA), skinfold thickness (SF) and dual-energy x-ray absorptiometry (DXA) in 10 subjects from HIV+LIPO+ group; 22 subjects from HIV+LIPO- group and 12 from Control group. Results: There were no differences in age and body mass index (BMI) between groups. The fat mass (FM) (%) estimated by SF did not correlate with DXA in HIV+LIPO+ group (r = 0,46/p >0,05) and had fair agreement in both HIV groups (HIV+LIPO+ =0,35/ HIV+ LIPO- = 0,40). BIA had significant correlation in all groups (p < 0,05) and strong agreement, meanly in HIV groups, for FM (HIV+LIPO+ = 0,79/ HIV+LIPO- = 0,85/Control = 0,60) and for fat free mass (FFM) (HIV+LIPO+ = 0,93/ HIV+LIPO- = 0,92 / Control = 0,73). Discussion: Total fat mass can be measured by BIA with good precision, but not by SF in HIV-infected patients with LS. Segmental BIA, triciptal SF, circumferences of arms, waist and legs maybe alternatives that need more studies.

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.

Frequency of HLA-B27 and its alleles in patients with Reiter syndrome: comparison with the frequency in other spondyloarthropathies and a healthy control population

This retrospective study analyzed the HLA-B*27 alleles in a group of 20 consecutive patients with the diagnosis of Reiter syndrome (RS) followed in a tertiary referral university hospital in Brazil, during the period 1990-2006, and compared the data with that observed in other patients with spondyloarthropathies followed at the same institution. Eight cases were associated to gastrointestinal infection, eight cases to previous urethritis, and four cases presented no established preceding infection. HLA-B*27 alleles were typed by polymerase chain reaction-amplified DNA hybridized with sequence-specific oligonucleotide probes (HLA-B*2701 to HLA-B*2721). They were compared to a group of 108 patients with ankylosing spondylitis (AS), 40 with undifferentiated spondyloarthropathy (uSpA) and 111 healthy controls. Among the 20 patients, 17 were HLA-B*27 positive (85%). Two HLA-B*27 alleles were observed: HLA-B*2705 (65%) and HLA-B*2702 (35%). In the other spondyloarthropathies, the observed alleles were HLA-B*2705 (90% in AS and 92.5% in uSpA), HLA-B*2702 (8% in AS and 5% in uSpA), HLA-B*2704 (1% in AS and 2.5% in uSpA) and HLA-B*2713 (1% in AS). Among the 111 healthy controls, 80% presented HLA-B*2705, followed by HLA-B*2702 in 10%, HLA-B*2703 in 6%, HLA-B*2707 in 3% and HLA-B*2713 in 1%. Concluding, in the HLA-B*27 positive patients with RS in this study there was predominance of HLA-B*2705 allele, in a lower frequency than that observed in patients with other spondyloarthropathies and healthy controls.

Cultural consonance and adult body composition in urban Brazil

In previous research in Brazil, we found socioeconomic and gender differences in body mass and percent body fat, consistent with a model in which individuals in higher socioeconomic strata, especially women, could achieve a cultural ideal of body size and shape. In this article, using new data, we examine these processes more precisely using measures of cultural consonance. Cultural consonance refers to the degree to which individuals approximate, in their own beliefs and behaviors, the shared prototypes for belief and behavior encoded in cultural models. We have found higher cultural consonance in several domains to be associated with health outcomes. Furthermore, there tends to be a general consistency in cultural consonance across domains. Here we suggest that measures of body composition can be considered indicators of individuals` success in achieving cultural ideals of the body, and that cultural consonance in several domains will be associated with body composition. Using waist circumference as an outcome, smaller waist size was associated with higher cultural consonance in lifestyle (beta = -0.311, P < 0.01) and higher cultural consonance in the consumption of high prestige foods (beta = -0.260, P < 0.01) for women (n = 161), but not for men (n = 106), controlling for age, family income, tobacco use, and dietary intake of protein and carbohydrates. Similar results were obtained using the body mass index and weight as outcomes, while there were no associations with height. These results help to illuminate the cultural mediation of body composition.

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.

Under-reporting of food intake is frequent among Brazilian free-living older persons: a doubly labelled water study

The assessment of food intake is essential for the development of dietetic interventions. Accuracy is low when intake is assessed by questionnaires, the under-reporting of food intake being frequent. Most such studies, however, were performed in developed countries and there is little data about the older population of developing nations. This study aimed to verify the total energy expenditure (TEE) of independent older Brazilians living in an urban area, through the doubly labelled water (DLW) method and to compare it with the reported energy intake obtained through the application of a food frequency questionnaire (FFQ). Initially, 100 volunteers aged from 60 to 75 years had their body composition determined by dual-energy X-ray absorptiometry (DEXA). Five volunteers of each quartile of body fat percentage had their energy expenditure determined by DLW. The mean age of the subjects included in this phase of the study was 66.4 +/- 3.5 years, and ten of the subjects were men. The mean TEE was 2565 +/- 614 and 2154 +/- 339 kcal.day(-1) for men and women, respectively. The Physical Activity Level (PAL) was 1.58 +/- 0.31 and 1.52 +/- 0.22, respectively. Under-reporting of food intake was highly prevalent, with a mean percentage of reported intake in relation to measured TEE of -17.7%. Thus, under-reporting of food intake is highly prevalent among Brazilian independent older persons. The DLW method is an important tool in nutritional studies and its use is to be recommended in developing countries. Copyright (C) 2010 John Wiley & Sons, Ltd.

Assessing Individual Interethnic Admixture and Population Substructure Using a 48-Insertion-Deletion (INSEL) Ancestry-Informative Marker (AIM) Panel

Estimating the proportions of different ancestries in admixed populations is very important in population genetics studies, and it is particularly important for detecting population substructure effects in case-control association studies. In this work, a set of 48 ancestry, informative insertion, deletion polymorphisms (INDELs) were selected with the goal of efficiently measuring the proportions of three different ancestries (sub-Saharan African, European, and Native American) in mixed populations. All selected markers can be easily analyzed via multiplex PCR and detected with standard capillary electrophoresis. A total of 593 unrelated individuals representative of European, African, and Native American parental populations were typed, as were 380 individuals from three Brazilian populations with known admixture patterns. As expected, the interethnic admixture estimates show that individuals from southern Brazil present an almost exclusively European ancestry; Afro-descendant communities in the Amazon region, apart from the major African contribution, present some degree of admixture with Europeans and Native Americans; and a sample from Belem, in the northeastern Amazon, shows a significant contribution of the three ethnic groups, although with a greater European proportion. In summary, a panel of ancestry-informative INDELs was optimized and proven to be a variable tool for estimating individual and global ancestry proportions in admixed populations. The ability to accurately infer interethnic admixtures highlights the usefulness of this marker set for assessing population substructure in association studies, particularly those conducted in Brazilian and other Latin American populations sharing trihybrid ancestry patterns. Hum Mutat 31:184-190, 2010. (C) 2009 Wiley-Liss, Inc.

Migration in Afro-Brazilian Rural Communities: Crossing Demographic and Genetic Data

Many studies have used genetic markers to understand global migration patterns of our species. However, there are only few studies of human migration on a local scale. We, therefore, researched migration dynamics in three Afro-Brazilian rural communities, using demographic data and ten Ancestry Informative Markers. In addition to the description of migration and marriage structures, we carried out genetic comparisons between the three populations, as well as between locals and migrants from each community. Genetic admixture analyses were conducted according to the gene-identity method, with Sub-Saharan Africans, Amerindians, and Europeans as parental populations. The three analyzed Afro-Brazilian rural communities consisted of 16% to 30% of migrants, most of them women. The age pyramid revealed a gap in the segment of men aged between 20 to 30 yrs. While endogamous marriages predominated, exogamous marriages were mainly patrilocal. Migration dynamics are apparently associated with matrimonial customs and other social practices of such communities. The impact of migration upon the populations` genetic composition was low but showed an increase in European alleles with a concomitant decrease in the Amerindian contribution. Admixture analysis evidenced a higher African contribution to the gene pool of the studied populations, followed by the contribution of Europeans and Amerindians, respectively.

Mitochondrial population genomics supports a single pre-Clovis origin with a coastal route for the peopling of the Americas

It is well accepted that the Americas were the last continents reached by modern humans, most likely through Beringia. However, the precise time and mode of the colonization of the New World remain hotly disputed issues. Native American populations exhibit almost exclusively five mitochondrial DNA (mtDNA) haplogroups (A-D and X). Haplogroups A-D are also frequent in Asia, suggesting a northeastern Asian origin of these lineages. However, the differential pattern of distribution and frequency of haplogroup X led some to suggest that it may represent an independent migration to the Americas. Here we show, by using 86 complete mitochondrial genomes, that all Native American haplogroups, including haplogroup X, were part of a single founding population, thereby refuting multiple-migration models. A detailed demographic history of the mtDNA sequences estimated with a Bayesian coalescent method indicates a complex model for the peopling of the Americas, in which the initial differentiation from Asian populations ended with a moderate bottleneck in Beringia during the last glacial maximum (LGM), around similar to 23,000 to similar to 19,000 years ago. Toward the end of the LGM, a strong population expansion started similar to 18,000 and finished similar to 15,000 years ago. These results support a pre-Clovis occupation of the New World, suggesting a rapid settlement of the continent along a Pacific coastal route.

Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus-immune maternal population

OBJECTIVE: To determine contribution of reinfection with new strains of cytomegalovirus in cytomegalovirus seromimmune women to incidence of congenital cytomegalovirus infection. STUDY DESIGN: In 7848 women studied prospectively for congenital cytomegalovirus infection from a population with near universal cytomegalovirus seroimmunity, sera from 40 mothers of congenitally infected infants and 109 mothers of uninfected newborns were analyzed for strain-specific anticytomegalovirus antibodies. RESULTS: All women were cytomegalovirus seroimmune at first prenatal visit. Reactivity for 2 cytomegalovirus strains was found in 14 of 40 study mothers and in 17 of 109 control mothers at first prenatal visit (P=.009). Seven of 40 (17.5%) study women and 5 of 109 (4.6%) controls (P=.002) acquired antibodies reactive with new cytomegalovirus strains during pregnancy. Evidence of infection with more than 1 strain of cytomegalovirus before or during current pregnancy occurred in 21 of 40 study mothers and 22 of 109 controls (P<.0001). CONCLUSION: Maternal reinfection by new strains of cytomegalovirus is a major source of congenital infection in this population.