Effect of race, genetic population structure, and genetic models in two-locus association studies: clustering of functional renin-angiotensin system gene variants in hypertension association studies

Previous genetic association studies have overlooked the potential for biased results when analyzing different population structures in ethnically diverse populations. The purpose of the present study was to quantify this bias in two-locus association studies conducted on an admixtured urban population. We studied the genetic structure distribution of angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen methionine/threonine (M/T) polymorphisms in 382 subjects from three subgroups in a highly admixtured urban population. Group I included 150 white subjects; group II, 142 mulatto subjects, and group III, 90 black subjects. We conducted sample size simulation studies using these data in different genetic models of gene action and interaction and used genetic distance calculation algorithms to help determine the population structure for the studied loci. Our results showed a statistically different population structure distribution of both ACE I/D (P = 0.02, OR = 1.56, 95% CI = 1.05-2.33 for the D allele, white versus black subgroup) and angiotensinogen M/T polymorphism (P = 0.007, OR = 1.71, 95% CI = 1.14-2.58 for the T allele, white versus black subgroup). Different sample sizes are predicted to be determinant of the power to detect a given genotypic association with a particular phenotype when conducting two-locus association studies in admixtured populations. In addition, the postulated genetic model is also a major determinant of the power to detect any association in a given sample size. The present simulation study helped to demonstrate the complex interrelation among ethnicity, power of the association, and the postulated genetic model of action of a particular allele in the context of clustering studies. This information is essential for the correct planning and interpretation of future association studies conducted on this population.

Genetic variability of a population of Aedes aegypti from Paraná, Brazil, using the mitochondrial ND4 gene

Genetic variability of a population of Aedes aegypti from Paraná, Brazil, using the mitochondrial ND4 gene. To analyze the genetic variability of populations of Aedes aegypti, 156 samples were collected from 10 municipalities in the state of Paraná, Brazil. A 311 base pairs (bp) region of the NADH dehydrogenase subunit 4 (ND4) mitochondrial gene was examined. An analysis of this fragment identified eight distinct haplotypes. The mean genetic diversity was high (h = 0.702; p = 0.01556). AMOVA analysis indicated that most of the variation (67%) occurred within populations and the F ST value (0.32996) was highly significant. F ST values were significant in most comparisons among cities. The isolation by distance was not significant (r = -0.1216 and p = 0, 7550), indicating that genetic distance is not related to geographic distance. Neighbor-joining analysis showed two genetically distinct groups within Paraná. The DNA polymorphism and AMOVA data indicate a decreased gene flow in populations from Paraná, which can result in increased vectorial competence.

Genetic Structure of Triatoma sordida (Hemiptera: Reduviidae) Domestic Populations from Bolivia: Application on Control Interventions

The genetic population of Triatoma sordida group 1, a secondary vector of Chagas disease in Bolivia, was studied by multi-locus enzyme electrophoresis. A total of 253 nymphal and adult specimens collected from seven neighbouring localities in the Velasco Province, Department of Santa Cruz, were processed. The relatively low genetic variability was confirmed for this species (rate of polymorphism: 0.20). The absence of genetic disequilibrium detected within the seven localities was demonstrated. A geographical structuration appears between localities with distances greater than 20 km apart. Although T. sordida presents a relatively reduced dispersive capacity, its panmictic unit is wider than compared with T. infestans. Genetic distances between T. sordida populations were correlated with geographic distance. Gene flow between geographic populations of T. sordida provides an efficient framework for effective vigilance and control protocols.

A combined approach of VNTR and MLST analysis: improving molecular typing of Argentinean isolates of Leptospira interrogans

Leptospirosis is an emerging infectious disease that has been identified as both a human and animal health problem worldwide. Regular outbreaks associated with specific risk factors have been reported in Argentina. However, there are no available data concerning the genetic population level for this pathogen. Therefore, the aim of this work was to describe the genetic diversity of Leptospira interrogans through the application of two molecular typing strategies: variable number of tandem repeats (VNTR) and multilocus sequence typing (MLST). For this purpose, seven reference strains and 18 non-epidemiologically related isolates from diverse hosts and Argentinean regions were analysed. Among them, nine genotypes and seven sequence types (STs), including three unreported STs, were described using VNTR and MLST, respectively. eBURST analysis demonstrated that ST37 was the most frequent and founder genotype of a clonal complex (CCs) containing STN1 and STN3, suggesting the importance of studying the serovars belonging to this CC in Argentina. The data from maximum parsimony analysis, which combined both techniques, achieved intra-serovar discrimination, surmounted microscopic agglutination test discrepancies and increased the discriminatory power of each technique applied separately. This study is the first to combine both strategies for L. interrogans typing to generate a more comprehensive molecular genotyping of isolates from Argentina in a global context.

Age transition of tuberculosis incidence and mortality in Brazil

OBJECTIVE: Before the Aids pandemic, demographic transition and control programs prompted a shift in the age of incidence of tuberculosis from adults to older people in many countries. The objective of the study is to evaluate this transition in Brazil. METHODS: Tuberculosis incidence and mortality data from the Ministry of Health and population data from the Brazilian Bureau of Statistics were used to calculate age-specific incidence and mortality rates and medians. RESULTS: Among reported cases, the proportion of older people increased from 10.5% to 12% and the median age from 38 to 41 years between the period of 1986 and 1996. The smallest decrease in the incidence rate occurred in the 30--49 and 60+ age groups. The median age of death increased from 53 to 55 years between 1980 and 1996. The general decline in mortality rates from 1986 to 1991 became less evident in the 30+ age group during the period of 1991 to 1996. A direct correlation between age and mortality rates was observed. The largest proportion of bacteriologically unconfirmed cases occurred in older individuals. CONCLUSIONS: The incidence of tuberculosis has begun to shift to the older population. This shift results from the decline in the annual risk of infection as well as the demographic transition. An increase in reactivation tuberculosis in older people is expected, since this population will grow from 5% to 14% of the Brazilian population over the next 50 years. A progressive reduction in HIV-related cases in adults will most likely occur. The difficulty in diagnosing tuberculosis in old age leads to increased mortality.

Disparities in cervical and breast cancer mortality in Brazil

OBJECTIVE To analyze cervical and breast cancer mortality in Brazil according to socioeconomic and welfare indicators. METHODS Data on breast and cervical cancer mortality covering a 30-year period (1980-2010) were analyzed. The data were obtained from the National Mortality Database, population data from the Brazilian Institute of Geography and Statistics database, and socioeconomic and welfare information from the Institute of Applied Economic Research. Moving averages were calculated, disaggregated by capital city and municipality. The annual percent change in mortality rates was estimated by segmented linear regression using the joinpoint method. Pearson’s correlation coefficients were conducted between average mortality rate at the end of the three-year period and selected indicators in the state capital and each Brazilian state. RESULTS There was a decline in cervical cancer mortality rates throughout the period studied, except in municipalities outside of the capitals in the North and Northeast. There was a decrease in breast cancer mortality in the capitals from the end of the 1990s onwards. Favorable socioeconomic indicators were inversely correlated with cervical cancer mortality. A strong direct correlation was found with favorable indicators and an inverse correlation with fertility rate and breast cancer mortality in inner cities. CONCLUSIONS There is an ongoing dynamic process of increased risk of cervical and breast cancer and attenuation of mortality because of increased, albeit unequal, access to and provision of screening, diagnosis and treatment. 

Hospitalizations for ambulatory care-sensitive conditions, Minas Gerais, Southeastern Brazil, 2000 and 2010

OBJECTIVE To analyze hospitalization rates and the proportion of deaths due to ambulatory care-sensitive hospitalizations and to characterize them according to coverage by the Family Health Strategy, a primary health care guidance program. METHODS An ecological study comprising 853 municipalities in the state of Minas Gerais, under the purview of 28 regional health care units, was conducted. We used data from the Hospital Information System of the Brazilian Unified Health System. Ambulatory care-sensitive hospitalizations in 2000 and 2010 were compared. Population data were obtained from the demographic censuses. RESULTS The number of ambulatory care-sensitive hospitalizations declined from 20.75/1,000 inhabitants [standard deviation (SD) = 10.42) in 2000 to 14.92/thousand inhabitants (SD = 10.04) in 2010 Heart failure was the most frequent cause in both years. Hospitalizations rates for hypertension, asthma, and diabetes mellitus, decreased, whereas those for angina pectoris, prenatal and birth disorders, kidney and urinary tract infections, and other acute infections increased. Hospitalization durations and the proportion of deaths due to ambulatory care-sensitive hospitalizations increased significantly. CONCLUSIONS Mean hospitalization rates for sensitive conditions were significantly lower in 2010 than in 2000, but no correlation was found with regard to the expansion of the population coverage of the Family Health Strategy. Hospitalization rates and proportion of deaths were different between the various health care regions in the years evaluated, indicating a need to prioritize the primary health care with high efficiency and quality.

Trends in mortality due to ischemic heart disease in the municipality of Goiania, Brazil, during the years between 1980 and 1994

OBJECTIVE: To analyze the trends of specific, standardized coefficients of mortality due to ischemic heart disease according to sex and age during the years 1980 and 1994 in the municipality of Goiania, GO, Brazil. METHODS: Data on deaths were retrieved from the Information on Mortality System of the Ministry of Health; population data were obtained from the Foundation of the Brazilian Institute for Geography and Statistics (IBGE). The trends of the specific coefficients were analyzed by triennia of the historical series, including individuals of both sexes from 25 years of age on, partitioned into 6 age groups of ten years intervals. The population data corresponding to the year 1980 were used as the standard for the calculation of each age group coefficient. Analyses were carried out by straight linear regression. RESULTS: Coefficients were greater for males in each triennium of the series and increased with age in both sexes. The study of the trends of the specific age coefficients of both sexes revealed a stable pattern of evolution up to the age of 65-74 years (P>0.05). From 75 years on, a clear-cut decline in mortality due to ischemic heart disease was shown by both sexes. The standardized coefficients also showed a significant decline (p<=0.05). CONCLUSION: The municipality of Goiânia is at present in a stage of epidemiological transition similar to that of developed countries, even though the observed decline is predominantly influenced by the mortality of older individuals (75 years of age or older).

Evolution of Cardiovascular Diseases Mortality in the Counties of the State of Rio de Janeiro from 1979 to 2010

Background: Cardiovascular Diseases (CVD) are the leading cause of death in Brazil. Objective: To estimate total CVD, cerebrovascular disease (CBVD), and ischemic heart disease (IHD) mortality rates in adults in the counties of the state of Rio de Janeiro (SRJ), from 1979 to 2010. Methods: The counties of the SRJ were analysed according to their denominations stablished by the geopolitical structure of 1950, Each new county that have since been created, splitting from their original county, was grouped according to their former origin. Population Data were obtained from the Brazilian Institute of Geography and Statistics (IBGE), and data on deaths were obtained from DataSus/MS. Mean CVD, CBVD, and IHD mortality rates were estimated, compensated for deaths from ill-defined causes, and adjusted for age and sex using the direct method for three periods: 1979–1989, 1990–1999, and 2000–2010, Such results were spatially represented in maps. Tables were also constructed showing the mortality rates for each disease and year period. Results: There was a significant reduction in mortality rates across the three disease groups over the the three defined periods in all the county clusters analysed, Despite an initial mortality rate variation among the counties, it was observed a homogenization of such rates at the final period (2000–2010). The drop in CBVD mortality was greater than that in IHD mortality. Conclusion: Mortality due to CVD has steadily decreased in the SRJ in the last three decades. This reduction cannot be explained by greater access to high technology procedures or better control of cardiovascular risk factors as these facts have not occurred or happened in low proportion of cases with the exception of smoking which has decreased significantly. Therefore, it is necessary to seek explanations for this decrease, which may be related to improvements in the socioeconomic conditions of the population.

Pulmonary Embolism Mortality in Brazil from 1989 to 2010: Gender and Regional Disparities

Abstract Background: A significant variation in pulmonary embolism (PE) mortality trends have been documented around the world. We investigated the trends in mortality rate from PE in Brazil over a period of 21 years and its regional and gender differences. Methods: Using a nationwide database of death certificate information we searched for all cases with PE as the underlying cause of death between 1989 and 2010. Population data were obtained from the Brazilian Institute of Geography and Statistics (IBGE). We calculated age-, gender- and region-specific mortality rates for each year, using the 2000 Brazilian population for direct standardization. Results: Over 21 years the age-standardized mortality rate (ASMR) fell 31% from 3.04/100,000 to 2.09/100,000. In every year between 1989 and 2010, the ASMR was higher in women than in men, but both showed a significant declining trend, from 3.10/100,000 to 2.36/100,000 and from 2.94/100,000 to 1.80/100,000, respectively. Although all country regions showed a decline in their ASMR, the largest fall in death rates was concentrated in the highest income regions of the South and Southeast Brazil. The North and Northeast regions, the lowest income areas, showed a less marked fall in death rates and no distinct change in the PE mortality rate in women. Conclusions: Our study showed a reduction in the PE mortality rate over two decades in Brazil. However, significant variation in this trend was observed amongst the five country regions and between genders, pointing to possible disparities in health care access and quality in these groups.

Trends in Mortality Rate from Cardiovascular Disease in Brazil, 1980-2012

Abstract Background: Studies have questioned the downward trend in mortality from cardiovascular diseases (CVD) in Brazil in recent years. Objective: to analyze recent trends in mortality from ischemic heart disease (IHD) and stroke in the Brazilian population. Methods: Mortality and population data were obtained from the Brazilian Institute of Geography and Statistics and the Ministry of Health. Risk of death was adjusted by the direct method, using as reference the world population of 2000. We analyzed trends in mortality from CVD, IHD and stroke in women and men in the periods of 1980-2006 and 2007-2012. Results: there was a decrease in CVD mortality and stroke in women and men for both periods (p < 0.001). Annual mortality variations for periods 1980-2006 and 2007-2012 were, respectively: CVD (total): -1.5% and -0.8%; CVD men: -1.4% and -0.6%; CVD women: -1.7% and -1.0%; DIC (men): -1.1% and 0.1%; stroke (men): -1.7% and -1.4%; DIC (women): -1.5% and 0.4%; stroke (women): -2.0% and -1.9%. From 1980 to 2006, there was a decrease in IHD mortality in men and women (p < 0.001), but from 2007 to 2012, changes in IHD mortality were not significant in men [y = 151 + 0.04 (R2 = 0.02; p = 0.779)] and women [y = 88-0.54 (R2 = 0.24; p = 0.320). Conclusion: Trend in mortality from IHD stopped falling in Brazil from 2007 to 2012.

Sensitivity reduction in Blumeria graminis f. sp. hordei to triadimenol fungicide applied as barley seed treatment

Experiments were carried out in a growth chamber with controlled temperature and photoperiod to test two populations of Blumeria graminis f. sp. hordei from Guarapuava, Paraná State, and Passo Fundo, Rio Grande do Sul State, Brazil. Treatments consisted in application of the fungicide triadimenol (Baytan 150 SC®) at three rates of its commercial formulation: 150, 250, 350 mL/100 Kg barley seeds. The experiments were conducted separately in a growth chamber for each population, adopting the same temperature and photoperiod. For inoculation, pots containing barley seedlings colonized by the fungus were placed among the plots. After emergence of the first symptoms, the disease severity was assessed at two-day intervals. The experiments were repeated twice for each fungus population. Data were expressed as area under the disease progress curve and as powdery mildew control by comparing the severity after the fungicide treatments to that of control. Data were subjected to analysis of variance and regression analysis; the area under the disease progress curve was also calculated. Comparing the data obtained in the present study with those reported in the literature and the control, the maximum value of 26.1% is considered insufficient to prevent the damages caused by the disease. The control response to the fungicide rate was significant. We can conclude that there was a reduction in the sensitivity of both B. graminis f.sp. hordei populations to the fungicide triadimenol, which explains the control failure observed in barley farms.

Population genetic structure of the major malaria vector Anopheles darlingi (Diptera: Culicidae) from the Brazilian Amazon, using microsatellite markers

The population genetic structure of Anopheles darlingi, the major human malaria vector in the Neotropics, was examined using seven microsatellite loci from nine localities in central and western Amazonian Brazil. High levels of genetic variability were detected (5-25 alleles per locus; H E = 0.519-0.949). There was deviation from Hardy-Weinberg Equilibrium for 59.79% of the tests due to heterozygote deficits, while the analysis of linkage disequilibrium was significant for only two of 189 (1.05%) tests, most likely caused by null alleles. Genetic differentiation (F ST = 0.001-0.095; Nm = 4.7-363.8) indicates that gene flow is extensive among locations < 152 km apart (with two exceptions) and reduced, but not absent, at a larger geographic scale. Genetic and geographic distances were significantly correlated (R² = 0.893, P < 0.0002), supporting the isolation by distance (IBD) model. The overall estimate of Ne was 202.4 individuals under the linkage disequilibrium model, and 8 under the heterozygote excess model. Analysis of molecular variance showed that nearly all variation (~ 94%) was within sample locations. The UPGMA phenogram clustered the samples geographically, with one branch including 5/6 of the state of Amazonas localities and the other branch the Acre, Rondônia, and remaining Amazonas localities. Taken together, these data suggest little genetic structure for An. darlingi from central and western Amazonian Brazil. These findings also imply that the IBD model explains nearly all of the differentiation detected. In practical terms, populations of An. darlingi at distances < 152 km should respond similarly to vector control measures, because of high gene flow.

Estimates of genetic and phenotypic parameters in a segregant population of rice irrigated by continuous flooding

Estimates of genetic and phenotypic parameters were obtained by using data from families of a recurrent selection program in rice. An experiment using population CNA-IRAT 4ME/1/1 was conducted at two locations (Lambari and Cambuquira) in the State of Minas Gerais, Brazil. At Lambari, families S0:2 and S0:3 were assessed during crop seasons 1992/1993 and 1993/1994, respectively. In the Cambuquira trial, only S0:3 families were tested in 1993/1994. The experimental design was a 10 x 10 lattice with three replications. The following traits were assessed: grain yield (GY), mean number of days to flowering (FL), plant height (PH), and the incidence of neck blast (NB) caused by Pyricularia grisea and grain staining (GS) caused by Drechslera oryzae. This population proved to be promising for recurrent selection, as it had high average yield and genetic variability. Heritability estimates obtained using variance components were generally greater than estimates of realized heritability, and heritability obtained by parent-offspring regression

Analysis of genetic relatedness between populations of Aedes aegypti from different geographic regions of São Paulo state, Brazil

RAPD markers have been used for the analysis of genetic differentiation of Aedes aegypti, because they allow the study of genetic relationships among populations. The aim of this study was to identify populations in different geographic regions of the São Paulo State in order to understand the infestation pattern of A. aegypti. The dendrogram constructed with the combined data set of the RAPD patterns showed that the mosquitoes were segregated into two major clusters. Mosquitoes from the Western region of the São Paulo State constituted one cluster and the other was composed of mosquitoes from a laboratory strain and from a coastal city, where the largest Latin American port is located. These data are in agreement with the report on the infestation in the São Paulo State. The genetic proximity was greater between mosquitoes whose geographic origin was closer. However, mosquitoes from the coastal city were genetically closer to laboratory-reared mosquitoes than to field-collected mosquitoes from the São Paulo State. The origin of the infestation in this place remains unclear, but certainly it is related to mosquitoes of origins different from those that infested the West and North region of the State in the 80's.