New insights on intercontinental origins of paternal lineages in Northeast Brazil.

BACKGROUND: The current Brazilian population is the product of centuries of admixture between intercontinental founding groups. Although previous results have revealed a heterogeneous distribution of mitochondrial lineages in the Northeast region, the most targeted by foreign settlers during the sixteenth century, little is known about the paternal ancestry of this particular population. Considering historical records have documented a series of territorial invasions in the Northeast by various European populations, we aimed to characterize the male lineages found in Brazilian individuals in order to discover to what extent these migrations have influenced the present-day gene pool. Our approach consisted of employing four hierarchical multiplex assays for the investigation of 45 unique event polymorphisms in the non-recombining portion of the Y-chromosome of 280 unrelated men from several Northeast Brazilian states. RESULTS: Primary multiplex results allowed the identification of six major haplogroups, four of which were screened for downstream SNPs and enabled the observation of 19 additional lineages. Results reveal a majority of Western European haplogroups, among which R1b-S116* was the most common (63.9%), corroborating historical records of colonizations by Iberian populations. Nonetheless, FST genetic distances show similarities between Northeast Brazil and several other European populations, indicating multiple origins of settlers. Regarding Native American ancestry, our findings confirm a strong sexual bias against such haplogroups, which represented only 2.5% of individuals, highly contrasting previous results for maternal lineages. Furthermore, we document the presence of several Middle Eastern and African haplogroups, supporting a complex historical formation of this population and highlighting its uniqueness among other Brazilian regions. CONCLUSIONS: We performed a comprehensive analysis of the major Y-chromosome lineages that form the most dynamic migratory region from the Brazilian colonial period. This evidence suggests that the ongoing entry of European, Middle Eastern, and African males in the Brazilian Northeast, since at least 500 years, was significantly responsible for the present-day genetic architecture of this population.

Topical application of cashew gum or chlorhexidine gel reduces overexpression of proinflammatory genes in experimental periodontitis.

This study aimed to explore the effect of topically administering an orabase gel containing cashew gum (CG), a complex polysaccharide from Anacardium occidentale L., on the transcription of important proinflammatory (COX-2, NOS-2, INF-γ, OSCAR, and MYD88) and anti-inflammatory genes (IL-10, IL-4, and TGFß1) in the gingival tissues of rats with ligature-induced periodontitis, compared to the effect observed upon topically applying a well-known antibiofilm agent (chlorhexidine) under the same experimental conditions. The gene expression profile in the gingival tissues of rats with periodontitis treated with CG did not statistically significantly differ from that observed in the group of animals treated with chlorhexidine. Results showed that CG is able to attenuate general inflammation in the periodontium by reducing the transcription of proinflammatory mediators in a MYD88-independent manner, and not by inducing the expression of anti-inflammatory factors. In conclusion, this study demonstrated that CG and chlorhexidine treatment reduced significantly the gene overexpression (COX-2, NOS-2, INF-γ, OSCAR, and TGFß1) in the model of ligature-induced periodontitis.

mtDNA structure: the women who formed the Brazilian Northeast.

BACKGROUND: The distribution of mitochondrial DNA (mtDNA) lineages in Brazil is heterogeneous due to different regional colonization dynamics. Northeastern Brazil, although being an important region in terms of human imigration and ethnic admixture, has little information regarding its population mtDNA composition. Here, we determine which mitochondrial lineages contributed to the formation of the Northeastern Brazilian population. Our sample consisted of 767 individuals distributed as follows i) 550 individuals from eight Northeastern states (Piauí, Ceará, Rio Grande do Norte, Paraíba, Pernambuco, Alagoas, Sergipe, and Bahia) which were sequenced for mtDNA hypervariable segments I, II, and III; ii) 217 individuals from Alagoas and Pernambuco (previously published data). Data analysis was performed through sequence alignment and Haplogrep 2.0 haplogroup assignment tools. Furthermore, maternal ancestry distribution was contextualized and, when possible, related to historical events to better understand the biological interactions and population dynamics that occurred in this region since the beginning of colonization. RESULTS: Unexpectedly, Amerindian mitochondrial ancestry was the highest in the Northeastern region overall, followed by African, European and non-Amerindian Asian, unlike previous results for this region. Alagoas and Pernambuco states, however, showed a larger African mtDNA frequency. The Northeastern region showed an intraregional heterogeneous distribution regarding ancestral groups, in which states/mesoregions located to the north had a prevalent Amerindian ancestral frequency and those to the south had predominance of African ancestry. Moreover, results showed great diversity of European haplogroups and the presence of non-Amerindian Asian haplogroups. CONCLUSIONS: Our findings are in disagreement with previous investigations that suggest African mitochondrial ancestry is the most prevalent in the Brazilian Northeast. The predominance of Amerindian lineages exemplifies the importance of indigenous women in the formation of the population, despite intense African slave entry and conflicts with European settlers. The variable distribution of ancestral groups observed in the Northeast is in accordance with historical records showing the similarities with colonization dynamics occurred in the Amazon region and the Brazilian Southeast. Moreover, the variety of European haplogroups suggests multiple origins of founding groups, specially those found in Western European populations.

Association study of the SLC6A3 VNTR (DAT) and DRD2/ANKK1 Taq1A polymorphisms with alcohol dependence in a population from northeastern Brazil.

BACKGROUND: Alcohol dependence (AD) is a complex psychiatric disorder, affecting 5.4% of the general population lifetime, characterized by excessive alcohol consumption influenced by environmental risk factors and genetic factors. Genetic alterations in dopaminergic system are involved in the treatment and etiology of AD. The aim of this search was to test the association of the SLC6A3 40 bp-VNTR and DRD2/ANKK1 Taq1A single nucleotide polymorphism (SNP), a transporter and receptor of the dopaminergic system, with AD through a study in a population of northeastern Brazil. METHODS: The study design was a case-control that included 227 males of northeastern Brazil (113 alcoholics and 114 controls). Alcoholics were classified according to the DSM-IV criteria for AD and controls were subjects who had nonalcohol problems or who never drank. Genotyping was detected through polymerase chain reaction (PCR) for SLC6A3 40 bp-VNTR and RFLP-PCR for DRD2/ANKK1 Taq1A, and subsequent electrophoresis on a 2% agarose gel. The distribution of allele and genotype frequencies and association of polymorphisms with AD were assessed by chi-square, Fisher's exact test, and odds ratio (OR) with a confidence interval of 95% and significance p < 0.05. Data were analyzed on BioEstat 5.3 software. RESULTS: The SLC6A3 40 bp-VNTR was associated with AD, allelic, and genotypic frequencies were significantly different, respectively (A9 vs. A10: OR = 1.88; p = 0.01; A9/A9 vs. A10/A10: OR = 6.25; p = 0.02; A9/A9 vs. A9/A10 + A10A10: OR = 5.44; p = 0.03). However, there was no statistically significant difference when the allelic (p = 0.10) and genotypic (p > 0.05) frequencies for DRD2/ANKK1 Taq1A were compared. CONCLUSIONS: These findings suggest that A9 allele and A9/A9 genotype of the SLC6A3 40 bp-VNTR are involved in the vulnerability to AD in the population studied. However, for the DRD2/ANKK1 SNP does not present contributions to the development of AD.

Brugada syndrome in a family with a high mortality rate: a case report.

INTRODUCTION: Brugada syndrome is a hereditary arrhythmia characterized by a specific electrocardiographic pattern and an increased risk of sudden cardiac death, with an apparent absence of structural abnormalities or ischemic heart disease. To date, mutations in the sodium channel, voltage-gated, type V, alpha subunit gene and glycerol-3-phosphate dehydrogenase 1-like gene are estimated to account for approximately 28% of Brugada syndrome probands. CASE PRESENTATION: We report the case of a 32-year-old mixed-race Brazilian man who is sodium channel, voltage-gated, type V, alpha subunit gene and glycerol-3-phosphate dehydrogenase 1-like gene mutation-negative with a type 1 Brugada electrocardiographic pattern and a history of high family mortality, including five sudden deaths among relatives of whom four were first-degree relatives. CONCLUSION: To the best of our knowledge, this is the first case of a patient who has Brugada syndrome and a history of sudden death in four first-degree family members. This case report reinforces the evidence that genetic studies are of limited use while determining risk but remain helpful for diagnosis, and that diagnosis via electrocardiography is of great importance in preventing adverse events and stratifying risk. Although there are several technologically advanced diagnostic tools, they might not be accessible in small towns and hospitals; however, a basic diagnostic tool like electrocardiography is easily accessible.

Prevalência do polimorfismo C677T do gene MTHFR em uma população de idosos / Prevalence of MTHFR C677T polymorphism in an elderly population

Objetivo: determinar a prevalência do polimorfismo MTHFR C677T em uma amostra de 200 idosos da cidade de Parnaíba-PI e comparar suas freqüências genotípicas e alélicas com as observadas em outras populações. Método: a presença dopolimorfismo MTHFR C677T foi determinada pela técnica de reação em cadeia da polimerase seguida por tratamentocom a enzima de restrição HinfI (PCR-RFLP), acompanhado de eletroforese em gel de poliacrilamida 8%, corado comnitrato de prata. Resultados: dos 200 indivíduos estudados, 120 (60%) apresentaram genótipo homozigoto normal (CC);63 (31,5%) foram heterozigotos (CT) e 17 (8,5%) mostraram-se homozigotos TT. A frequência do alelo polimórfico T foide 23,4%. As frequências genotípicas mostraram-se sob equilíbrio de Hardy-Weinberg e não houve diferenças estatisticamentesignificantes quanto à distribuição do alelo T por sexo ou faixa etária. Conclusão: os resultados apresentadosneste estudo representam o primeiro relato indicativo da frequência deste polimorfismo em uma população piauiense. Afrequência do alelo T foi consideravelmente elevada (24,3%) comparada com a população geral e, portanto, estudos sãonecessários para investigar a contribuição desse polimorfismo na etiologia e/ou gravidade a determinadas doenças, nessapopulação.

Objective: to determine the prevalence of MTHFR C677T polymorphism in a sample of 200 elderly individuals fromParnaíba, Piauí, Brazil and to compare its genotypic and allelic frequencies with those observed in other populations.Method: the presence of MTHFR C677T polymorphism was evaluated by polymerase chain reaction followed by restrictionenzyme analysis with HinfI endonuclease (PCR-RFLP). After cleavage, the genotypes were evaluated by 8% silverstained polyacrylamide gel. Results: of the 200 individuals studied, 120 (60%) were homozygous normal (CC), 63 (31.5%) were heterozygous (CT) and 17 (8.5%) were homozygous TT. The frequency of the polymorphic allele T was23.4%. The genotypic frequencies were found to be in Hardy-Weinberg equilibrium and there was no statistically significantdifferences regarding the distribution of T-allele by sex or age. Conclusion: the results presented in this studyrepresent the first report of the MTHFR C677T polymorphism frequency in a population of Piauí. The T-allele frequencywas significantly higher (24.3%) compared to the general population and therefore studies are needed to investigate thecontribution of this polymorphism in the etiology and/or severity of certain diseases in this population

Epidemiologia do envelhecimento: dinamização, problemas e consequências / Epidemiology of aging: dynamization, problems and consequences

O presente trabalho objetiva descrever o perfil multidimensional dos idosos da cidade de Parnaíba, Piauí, frente aos hábitos de vida, condições de moradia, saneamento e outros indicadores de saúde. Foram recrutados 454 indivíduos com idade igual ou superior a 65 anos, de ambos os sexos. Obtiveram-se resultados preocupantes quanto ao grau de insalubridade e precários hábitos de higiene. Conclui-se que as condições de vida dos idosos predispõem o surgimento de vários agravos à saúde.(AU)

To describe a multidimensional profile of elderly Parnaíba, Piauí, compared to lifestyle, living conditions and sanitation, among other health indicators. We recruited 454 individuals aged over 65 years, of both sexes. The analyzed data showed worrying results regarding the degree of unhealthiness and poor hygiene habits. We conclude that the living conditions of the elderly predispose the emergence of several health problems.(AU)

Epidemiologia do envelhecimento: dinamização, problemas e consequências / Epidemiology of aging: dynamization, problems and consequences

O presente trabalho objetiva descrever o perfil multidimensional dos idosos da cidade de Parnaíba, Piauí, frente aos hábitos de vida, condições de moradia, saneamento e outros indicadores de saúde. Foram recrutados 454 indivíduos com idade igual ou superior a 65 anos, de ambos os sexos. Obtiveram-se resultados preocupantes quanto ao grau de insalubridade e precários hábitos de higiene. Conclui-se que as condições de vida dos idosos predispõem o surgimento de vários agravos à saúde...

To describe a multidimensional profile of elderly Parnaíba, Piauí, compared to lifestyle, living conditions and sanitation, among other health indicators. We recruited 454 individuals aged over 65 years, of both sexes. The analyzed data showed worrying results regarding the degree of unhealthiness and poor hygiene habits. We conclude that the living conditions of the elderly predispose the emergence of several health problems...

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.

CYP21 gene mutations in Brazilian patients with 21-hydroxylase deficiency from the Amazon region

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (P450c21, CYP21) accounts for about 95 percent of all CAH cases. The incidence of CYP21 gene mutations has been extensively studied in the last years, but in Brazil it has been investigated only in Southeast Brazilian patients. This study is the first report on the distribution of CYP21 mutations in patients from the Amazon region. Direct sequencing of the CYP21 gene identified at least one mutation in 96 percent of the studied chromosomes. The most common mutations found were IVS2-13A/C > G (36 percent), Q318X (12 percent), V281L (12 percent), 1760_1761insT (9 percent), Cluster E6 (7 percent), and P30L (7 percent). The worldwide most common mutations were identified among patients from the Amazon region at frequencies that may be expected for a population resulting from the admixture of Europeans (predominantly Portuguese), African Blacks and Amerindians, in proportions that differ from those estimated for South Brazilian populations. Interethnic mixture may explain the differences in the frequencies of some mutations between Brazilian patients from the Amazon and from the Southeast of the country. However, the differences found may also be due to variation in the number of patients with the different clinical forms of 21-hydroxylase deficiency in the studies carried out so far.

Prevalence of hereditary risk factors for thrombophilia in Belém, Brazilian Amazon

Different risk factors for venous thromboembolism (VTE) have been identified, including hereditary abnormalities in the mechanisms of coagulation and fibrinolysis. We investigated five genetic polymorphisms (FVL G1691A, FII G20210A, MTHFR C677T, TAFI A152G and TAFI T1053C) associated with VTE in individuals from the city of Belém in the Brazilian Amazon who had no history of VTE. No significant difference was found between the observed and expected genotype frequencies for the loci analyzed. We found high frequencies of MTHFR C677T (33.9 percent) and TAFI T1053C (74 percent) and low frequencies of FVL (1.6 percent), FII G20210A (0.8 percent) and TAFI A152G (0.8 percent). The FVL G1691A, FII G20210A and MTHFR C677T frequencies were similar to those for European populations and populations of European descent living in the city of Ribeirão Preto in the Brazilian state of São Paulo. The frequency of the two TAFI mutations in the Belém individuals was not significantly different from that described for individuals from Ribeirão Preto. We suggest that the risks for VTE in the population of Belém are of the same magnitude as that observed in European populations and in populations with an expressive European contribution.