Global pharmacogenomics: Impact of population diversity on the distribution of polymorphisms in the CYP2C cluster among Brazilians

The impact of biogeographical ancestry, self-reported 'race/color' and geographical origin on the frequency distribution of 10 CYP2C functional polymorphisms (CYP2C8*2, *3, *4, CYP2C9*2, *3, *5, *11, CYP2C19*2, *3 and *17) and their haplotypes was assessed in a representative cohort of the Brazilian population (n = 1034). TaqMan assays were used for allele discrimination at each CYP2C locus investigated. Individual proportions of European, African and Amerindian biogeographical ancestry were estimated using a panel of insertion-deletion polymorphisms. Multinomial log-linear models were applied to infer the statistical association between the CYP2C alleles and haplotypes (response variables), and biogeographical ancestry, self-reported Color and geographical origin (explanatory variables). The results showed that CYP2C19*3, CYP2C9*5 and CYP2C9*11 were rare alleles (<1%), the frequency of other variants ranged from 3.4% (CYP2C8*4) to 17.3% (CYP2C19*17). Two distinct haplotype blocks were identified: block 1 consists of three single nucleotide polymorphisms (SNPs) (CYP2C19*17, CYP2C19*2 and CYP2C9*2) and block 2 of six SNPs (CYP2C9*11, CYP2C9*3, CYP2C9*5, CYP2C8*2, CYP2C8*4 and CYP2C8*3). Diplotype analysis generated 41 haplotypes, of which eight had frequencies greater than 1% and together accounted for 96.4% of the overall genetic diversity. The distribution of CYP2C8 and CYP2C9 (but not CYP2C19) alleles, and of CYP2C haplotypes was significantly associated with self-reported Color and with the individual proportions of European and African genetic ancestry, irrespective of Color self-identification. The individual odds of having alleles CYP2C8*2, CYP2C8*3, CYP2C9*2 and CYP2C9*3, and haplotypes including these alleles, varied continuously as the proportion of European ancestry increased. Collectively, these data strongly suggest that the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of pharmacogenomic studies of the CYP2C cluster in order to avoid spurious conclusions based on improper matching of study cohorts. This conclusion extends to other polymorphic pharmacogenes among Brazilians, and most likely to other admixed populations of the Americas. The Pharmacogenomics Journal (2012) 12, 267-276; doi: 10.1038/tpj.2010.89; published online 21 December 2010

Spatial distribution of arboviral mosquito vectors (Diptera, Culicidae) in Vale do Ribeira in the South-eastern Brazilian Atlantic Forest

Mosquitoes are vectors of arboviruses that can cause encephalitis and hemorrhagic fevers in humans. Aedes serratus (Theobald), Aedes scapularis (Rondani) and Psorophora ferox (Von Humboldt) are potential vectors of arboviruses and are abundant in Vale do Ribeira, located in the Atlantic Forest in the southeast of the State of Sao Paulo, Brazil. The objective of this study was to predict the spatial distribution of these mosquitoes and estimate the risk of human exposure to mosquito bites. Results of the analyses show that humans are highly exposed to bites in the municipalities of Cananeia, Iguape and Ilha Comprida. In these localities the incidence of Rocio encephalitis was 2% in the 1970s. Furthermore, Ae. serratus, a recently implicated vector of yellow fever virus in the State of Rio Grande do Sul, should be a target for the entomological surveillance in the southeastern Atlantic Forest. Considering the continental dimensions of Brazil and the inherent difficulties in sampling its vast area, the habitat suitability method used in the study can be an important tool for predicting the distribution of vectors of pathogens.

Distribution of the CCR5delta32 allele (gene variant CCR5) in Rondonia, Western Amazonian region, Brazil

Since around 1723, on the occasion of its initial colonization by Europeans, Rondonia has received successive waves of immigrants. This has been further swelled by individuals from northeastern Brazil, who began entering at the beginning of the twentieth century. The ethnic composition varies across the state according to the various sites of settlement of each wave of immigrants. We analyzed the frequency of the CCR5 Delta 32 allele of the CCR5 chemokine receptor, which is considered a Caucasian marker, in five sample sets from the population. Four were collected in Porto Velho, the state capital and the site of several waves of migration. Of these, two, from the Hospital de Base were comprised of HB Mothers and HB Newborns presenting allele frequencies of 3.5% and 3.1%, respectively, a third from the peri-urban neighborhoods of Candelaria/Bate-Estaca (1.8%), whereas a fourth, from the Research Center on Tropical Medicine/CEPEM (0.6%), was composed of malaria patients under treament. The fifth sample (3.4%) came from the inland Quilombola village of Pedras Negras. Two homozygous individuals (CCR5 Delta 32/CCR5 Delta 32) were detected among the HB Mother samples. The frequency of this allele was heterogeneous and higher where the European inflow was more pronounced. The presence of the allele in Pedras Negras revealed European miscegenation in a community largely comprising Quilombolas.

Regional and socioeconomic distribution of household food availability in Brazil, in 2008-2009

OBJECTIVE: To describe the regional and socioeconomic distribution of household food availability in Brazil. METHODS: Data from the 2008-2009 Household Budget Survey on food and beverage acquisition for household consumption, conducted by the Instituto Brasileiro de Geografia e Estatistica (Brazilian Institute of Geography and Statistics), were analyzed. The amounts of foods, recorded during seven consecutive days in the 55,970 sample households, were converted into calories and nutrients. Food quality indicators were constructed and analyzed according to the regional and socioeconomic strata of the Brazilian population. RESULTS: The amount of energy from protein was adequate in all regional and socioeconomic strata. On the other hand, an excess of free sugars and fats was observed in all regions of the country, especially in the Southern and Southeastern regions. The proportion of saturated fats was high in urban areas and consistent with the greater contribution of animal-derived products. Limited availability of fruits and vegetables was found in all regions. An increase in the fat content and reduction in carbohydrate content of the diet were observed with the increase in income. CONCLUSIONS: The negative characteristics of the Brazilian diet observed at the end of the first decade of the 21(st) century indicate the need to prioritize public policies for the promotion of healthy eating.

Pontomedullary and hypothalamic distribution of Fos-like immunoreactive neurons after acute exercise in rats

During exercise, intense brain activity orchestrates an increase in muscle tension. Additionally, there is an increase in cardiac output and ventilation to compensate the increased metabolic demand of muscle activity and to facilitate the removal of CO2 from and the delivery of O-2 to tissues. Here we tested the hypothesis that a subset of pontomedullary and hypothalamic neurons could be activated during dynamic acute exercise. Male Wistar rats (250-350 g) were divided into an exercise group (n = 12) that ran on a treadmill and a no-exercise group (n = 7). Immunohistochemistry of pontomedullary and hypothalamic sections to identify activation (c-Fos expression) of cardiorespiratory areas showed that the no-exercise rats exhibited minimal Fos expression. In contrast, there was intense activation of the nucleus of the solitary tract, the ventrolateral medulla (including the presumed central chemoreceptor neurons in the retrotrapezoid/parafacial region), the lateral parabrachial nucleus, the Kolliker-Fuse region, the perifornical region, which includes the perifornical area and the lateral hypothalamus, the dorsal medial hypothalamus, and the paraventricular nucleus of the hypothalamus after running exercise. Additionally, we observed Fos immunoreactivity in catecholaminergic neurons within the ventrolateral medulla (C1 region) without Fos expression in the A2, A5 and A7 neurons. In summary, we show for the first time that after acute exercise there is an intense activation of brain areas crucial for cardiorespiratory control. Possible involvement of the central command mechanism should be considered. Our results suggest whole brain-specific mobilization to correct and compensate the homeostatic changes produced by acute exercise. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Modeling the Potential Geographic Distribution of Black Pepper (Piper nigrum) in Asia Using GIS Tools

Known as the "king of spices", black pepper (Piper nigrum), a perennial crop of the tropics, is economically the most important and the most widely used spice crop in the world. To understand its suitable bioclimatic distribution, maximum entropy based on ecological niche modeling was used to model the bioclimatic niches of the species in its Asian range. Based on known occurrences, bioclimatic areas with higher probabilities are mainly located in the eastern and western coasts of the Indian Peninsula, the east of Sumatra Island, some areas in the Malay Archipelago, and the southeast coastal areas of China. Some undocumented places were also predicted as suitable areas. According to the jackknife procedure, the minimum temperature of the coldest month, the mean monthly temperature range, and the precipitation of the wettest month were identified as highly effective factors in the distribution of black pepper and could possibly account for the crop's distribution pattern. Such climatic requirements inhibited this species from dispersing and gaining a larger geographical range.

A model of road effect using line integrals and a test of the performance of two new road indices using the distribution of small mammals in an Atlantic Forest landscape

Effects of roads on wildlife and its habitat have been measured using metrics, such as the nearest road distance, road density, and effective mesh size. In this work we introduce two new indices: (1) Integral Road Effect (IRE), which measured the sum effects of points in a road at a fixed point in the forest; and (2) Average Value of the Infinitesimal Road Effect (AVIRE), which measured the average of the effects of roads at this point. IRE is formally defined as the line integral of a special function (the infinitesimal road effect) along the curves that model the roads, whereas AVIRE is the quotient of IRE by the length of the roads. Combining tools of ArcGIS software with a numerical algorithm, we calculated these and other road and habitat cover indices in a sample of points in a human-modified landscape in the Brazilian Atlantic Forest, where data on the abundance of two groups of small mammals (forest specialists and habitat generalists) were collected in the field. We then compared through the Akaike Information Criterion (AIC) a set of candidate regression models to explain the variation in small mammal abundance, including models with our two new road indices (AVIRE and IRE) or models with other road effect indices (nearest road distance, mesh size, and road density), and reference models (containing only habitat indices, or only the intercept without the effect of any variable). Compared to other road effect indices, AVIRE showed the best performance to explain abundance of forest specialist species, whereas the nearest road distance obtained the best performance to generalist species. AVIRE and habitat together were included in the best model for both small mammal groups, that is, higher abundance of specialist and generalist small mammals occurred where there is lower average road effect (less AVIRE) and more habitat. Moreover, AVIRE was not significantly correlated with habitat cover of specialists and generalists differing from the other road effect indices, except mesh size, which allows for separating the effect of roads from the effect of habitat on small mammal communities. We suggest that the proposed indices and GIS procedures could also be useful to describe other spatial ecological phenomena, such as edge effect in habitat fragments. (C) 2012 Elsevier B.V. All rights reserved.

Water balance and spatial distribution of an anuran community from Brazil

Terrestrial amphibians may dehydrate when exposed to low humidity, representing an important factor affecting spatial distribution and community composition. In this study we investigated whether rates of dehydration and rehydration are able to explain the spatial distribution of an anuran community in a Restinga environment at the northern coast of the State of Bahia, Brazil, represented by 11 species distributed in 27 sample units. The environmental data set containing 20 variables was reduced to a few synthetic axes by principal component analysis (PCA). Physiological variables measured were rates of dehydration, rehydration from water, and rehydration from a neutral substrate. Multiple regression analyses were used to test the null hypothesis of no association between the environmental data set (synthetic axes of PCA) and each axis representative of a physiological variable, which was rejected (P < 0.001). Of 15 possible partial regressions only rehydration rate from neutral substrate vs. PC1. and PC2, rehydration rate from water vs. PC1, and dehydration rate vs. PC2 were significant. Our analysis was influenced by a gradient between two different groups of sample units: a beach area with high density of bromeliads and an environment without bodies of water with low density of bromeliads. Species of very specific natural history and morphological characters occur in these environments: Phyllodytes melanomystax and Scinax auratus, species frequently occurring in terrestrial bromeliads, and Ischnocnema paulodutrai, common along the northern coast of Bahia and usually found in forest remnants within environments with low number of bodies of water. In dry environments species with lower rates of dehydration were dominant, whereas species showing greater rates of dehydration were found predominantly in microhabitats with greater moisture or abundance of bodies of water.

Seasonal Distribution of Airborne Trace Elements and Water-Soluble Ions in Sao Paulo Megacity, Brazil

This study deals with the seasonal distribution of Al, Ca, Cu, Fe, K, Mg, Na, Pb and Zn and water soluble ions (Cl-, PO43-, NO3-, SO42-, HCOO-, CH3COO-, oxalate, succinate, Na+, NH4+, K+, Mg2+ and Ca2+) found in PM10 samples (particulate matter less than 10 mu m in diameter) Sao Paulo City, Brazil, (April 2003-May 2004). Higher atmospheric levels were found for SO42-, NO3-, Cl- and PO43- while the main organic anions were oxalate and formate. Atmospheric levels for elements were: Fe > Al > Ca > K > Na > Mg > Zn > Cu > Pb. Some sources were predominant for some species: (i) fuel burning and/or biomass burning (NO3-, HCOO-, C2O42-, K+, Mg2+, Ca2+, Fe, Pb, Zn, Al, Ca, K and Mg), (ii) gas-to-particle conversion (SO42- and NH4+) and (iii) sea salt spray (Cl-, Na+ and Na).

Influence of Genomic Ancestry on the Distribution of SLCO1B1, SLCO1B3 and ABCB1 Gene Polymorphisms among Brazilians

The frequency distribution of SNPs and haplotypes in the ABCB1, SLCO1B1 and SLCO1B3 genes varies largely among continental populations. This variation can lead to biases in pharmacogenetic studies conducted in admixed populations such as those from Brazil and other Latin American countries. The aim of this study was to evaluate the influence of self-reported colour, geographical origin and genomic ancestry on distributions of the ABCB1, SLCO1B1 and SLCO1B3 polymorphisms and derived haplotypes in admixed Brazilian populations. A total of 1039 healthy adults from the north, north-east, south-east and south of Brazil were recruited for this investigation. The c.388A>G (rs2306283), c.463C>A (rs11045819) and c.521T>C (rs4149056) SNPs in the SLCO1B1 gene and c.334T>G (rs4149117) and c.699G>A (rs7311358) SNPs in the SLCO1B3 gene were determined by Taqman 5'-nuclease assays. The ABCB1 c.1236C>T (rs1128503), c.2677G>T/A (rs2032582) and c.3435C>T (rs1045642) polymorphisms were genotyped using a previously described single-base extension/termination method. The results showed that genotype and haplotype distributions are highly variable among populations of the same self-reported colour and geographical region. However, genomic ancestry showed that these associations are better explained by a continuous variable. The influence of ancestry on the distribution of alleles and haplotype frequencies was more evident in variants with large differences in allele frequencies between European and African populations. Design and interpretation of pharmacogenetic studies using these transporter genes should include genomic controls to avoid spurious conclusions based on improper matching of study cohorts from Brazilian populations and other highly admixed populations.