Association between interleukin 6 gene haplotype and Alzheimer's disease: a Brazilian case-control study.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that takes the form of a local overexpression of cytokines and other inflammatory molecules. We investigated three single-nucleotide polymorphisms (SNP) of the interleukin 6 gene (IL-6) promoter region [-174G/C (rs 1800795), -572C/G (rs 1800796), and -597G/A (rs 1800797)] in 200 patients with late-onset AD and 165 elderly controls in a Brazilian case-control population sample. Genotyping was carried out from blood cells using PCR-RFLP techniques. Statistical analysis was performed to evaluate the Hardy-Weinberg equilibrium and to compare frequencies between groups. No association was found between any IL-6 polymorphism and AD; however the haplotype composed of the -597 A allele and the -174G allele indicated a crude odds ratio (OR) of 0.15 (p = 0.0021) and a significantly adjusted OR (adjusted for the APOE E4 allele value) of 0.15 (p = 0.00294). Linkage disequilibrium was D' = 0.68 among the three SNPs. Our findings revealed a protective effect of AG (-597A, -174G) haplotype, which worked independently of the APOE E4 allele in our Brazilian population sample. Thus, the promoter region of IL-6 gene probably exerts an effect through gene linkage and/or gene interaction.

Major gene and multifactorial inheritance of mandibular prognathism.

Mandibular prognathism typically shows familial aggregation. Various genetic models have been described and it is assumed to be a multifactorial and polygenic trait, with a threshold for expression. Our goal was to examine specific genetic models of the familial transmission of this trait. The study sample comprised of 2,562 individuals from 55 families. Complete family histories for each proband were ascertained and the affection status of relatives were confirmed by lateral cephalograms, photographs, and dental models. Pedigrees were drawn using PELICAN and complex segregation analysis was performed using POINTER. Parts of some pedigrees were excluded to create one founder pedigrees, so the total N was 2,050. Analysis showed more affected females than males (P = 0.030). The majority of the pedigrees suggest autosomal dominant inheritance. Incomplete penetrance was demonstrated by the ratio of affected/unaffected parents and siblings. The heritability of mandibular prognathism was estimated to be 0.316. We conclude that there is a major gene that influences the expression of mandibular prognathism with clear signs of Mendelian inheritance and a multifactorial component.

Cell death and regeneration in the midgut of the mosquito, Culex quinquefasciatus.

Haematophagy, the utilization of blood as food, has evolved independently among insects such as mosquitoes, bedbugs, fleas, and others. Accordingly, several distinct biological adaptations have occurred in order to facilitate the finding, ingestion and digestion of blood from vertebrate sources. Although blood meals are essential for survival and reproduction of these insects, mechanical and chemical stresses are caused by the ingestion of a sizable meal (frequently twice or more times the weight of the insect) containing large amounts of cytotoxic molecules such as haem. Here we present data showing that the stresses caused by a blood meal induce cell death in the midgut epithelium of Culex quinquefasciatus mosquitoes. The process involves apoptosis, ejection of dead cells to the midgut lumen and differentiation of basal regenerative cells to replace the lost digestive cells. The basal cell differentiation in blood-fed mosquito midguts represents an additional mechanism by which insects cope with the stresses caused by blood meals. C. quinquefasciatus adult females are unable to replace lost cells following a third or fourth blood meal, which may have a significant impact on mosquito longevity, reproduction and vectorial capacity.

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms in a Brazilian mixed population.

The GSTM1 and GSTT1 null genotype frequencies were significantly different between 658 nonblack and black healthy blood donors from a Brazilian mixed population (Rio de Janeiro). The GSTM1 phenotype distribution was not in Hardy-Weinberg equilibrium in either group, mainly because of an excess of the GSTM1*A/*B genotype.

High prevalence of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in native Amazonian populations.

The epidemiology of malaria in 2 riverine localities in Rondjnia, Brazilian western Amazjnia, was assessed by a 1-year study at Portuchuelo, and a cross-sectional survey at riverine communities at Rio Machado (= Ji-Parana). Plasmodium spp. infections were diagnosed by light microscopy and by polymerase chain reaction (PCR) amplification of ribosomal DNA. PCR was 6-7 times more efficient than microscopy for detecting plasmodial infections. Both Plasmodium vivax and Plasmodium falciparum infections occurred as asymptomatic and symptomatic forms of the disease. The relation between symptomatic and asymptomatic clinical forms was roughly similar for both species of Plasmodium. Symptomless patients were monitored for 2 months. The prevalence of symptomless infections was 4-5 times higher than the symptomatic ones--respectively, 20% and 4.6% for Portuchuelo and 49.5% and 10% for Ji-Parana. Symptomatic malaria occurred mostly in patients in younger age groups. In contrast, there was a significant association of symptomless malaria with older age groups (medians of 26.5 and 21 years, respectively, for Portuchuelo and Ji-Parana), whereas the age medians for symptomatic malaria were 14 and 8 years, respectively, in the 2 regions. Symptomatic malaria also was more prevalent in groups living for shorter times in Amazjnia (13 and 4 years, respectively, for Portuchuelo and Ji-ParanA) as compared with symptomless malaria, which was more prevalent in groups living for longer periods in the region (medians of 25.5 and 18 years, respectively, for Portuchuelo and Ji-Paraná). The high prevalence of symptomless malaria may pose new problems for the currently adopted strategy for the control of malaria in the Amazonian region, which is essentially based on the treatment of symptomatic patients.

No evidence of linkage between Mitsuda reaction and the NRAMP1 locus

Thirty sib-pairs were ascertained through unrelated lepromatous probands. They consisted of 22 healthy individuals and 8 leprosy patients. The Mitsuda reactions of all sibs were evaluated both macroscopically and histologically, and high molecular weight genomic DNA was extracted from the white blood cells of all sib-pairs. Three DNA polymorphisms identified by polymerase chain reaction (274C/T, D543N, 1729 + 55del4) were used as chromosome markers at the NRAMP1 locus. Sib-pair comparisons did not disclose any sign of close linkage between the Mitsuda reaction and the genetic markers.

Malaria control in an agro-industrial settlement of Rondônia (Western Amazon region, Brazil)

A malaria control pilot project was developed in the Urupá agro-industrial farm that is situated in the State of Rondônia (Western Amazon Region, Brazil). Around 180 inhabitants had been surveyed for the past five years. The control measures were based on (1) training a community agent to perform on the spot microscopical diagnosis of malaria and to treat the uncomplicated cases of malaria; (2) limiting the use of insecticides to a short period before the high transmission season. This resulted in a significant reduction in the time between the onset of clinical symptoms and specific chemotherapy which fell from 3.5 to 1.3 days. In relation to the previous three reference years the total number of malaria cases was reduced to 50 in the first year and to 25 in the second year. The introduction of these measures coincided with pronounced reduction in the frequency of Plasmodium falciparum infections but this was less marked for P. vivax infections. In the second year of the pilot experiment there was no P. falciparum transmission on the farm. During the last decade there was a general decrease in the endemicity of malaria in the State of Rondônia. The linear regression coefficient values indicate that the decline was more pronounced in Urupá than in the general municipality and that the falciparum malaria API in Urupá farm is significantly lower than in the general municipality of Candeias were the farm is situated.

Evidence for biological inheritance of the eosinophil response to internal parasites in southeastern Brazil

Uma amostra de 177 indivíduos pertencentes a 120 famílias nucleares, completas ou incompletas, de Bambui, Estado de Minas Gerais, sudeste do Brasil, foi estudada com o objetivo de apurar algumas das causas da variabilidade da taxa de eosinófilos em pessoas parasitadas por vermes intestinais com ciclo de vida extra-digestivo. A análise de segregaçäo, aplicada aos dados sem correçäo para a assimetria, mostrou que a hipótese de um gene principal aditivo é consistente com os dados, enquanto que as hipóteses que supöem a açäo de um gene dominante, de um gene recessivo ou ainda herança multifatorial näo explicam, adequadamente, a significante agregaçäo familial observada. A correçäo mais parcimoniosa para assimetria mostrou resultados semelhantes, mas näo permitiu a distinçäao entre os modelos dominante e recessivo, embora permitisse a rejeiçäo do modelo codominante. Considerando que esse modelo supöe ser a assimetria devida ao entrelaçamento de duas distribuiçöes, esses resultados parecem concordar com aqueles obtidos quando os dados näo foram corrigidos. Pode-se sugerir que o papel desempenhado por vários fatores genéticos independentes na resistência/suscetibilidade à infestaçäo por helmintos seja determinado, principalmente, por suas capacidades de agir no estabelecimento de uma resposta eosinofílica.

Genetic epidemiology of infectious disease

The genetic mechanisms involved in the variability of the human response to the infection of some organisms are critically reviewed. For leprosy and leishmaniasis there seems to exist no simple and general mechanism. The Mitsuda reaction, however, seems to be the most important phenotype measuring the human response to M. leprae. Several genes are known to affect the resistance/susceptibility to malaria. Studies on this disease should take into account all of this variability and be particularly cautious regarding the natural history of the population under study in order to establish the relative importance of given genes on a given population subject to a give epidemic. The sole parasitic disease that did not show discrepancies among studies is schistosomiasis, indicating the importance of a single additive gene that, ultimately, acts on the individualïs capacity to build and efficient eosinophilia. Future studies should focus on general mechanisms as well as on explanations of the existent disparities between studies.

Genetic causes involved in Leishmania Chagasi infection innortheastern: Brazil

A sample of 502 individuals from 94 families from Jacobina, State of Bahia, Brazil, was investigated to determine the causal mechanisms involved in Leishmania chagasi (the causal agent of visceral leishmaniasis in the American hemisphere) infection, as measured by the intradermic reaction to antigens derived from this parasite, using complex segregation analyses. The results showed evidence of a major genetic mechanism acting on infection, with a frequency of a recessive (or additive) susceptibility gene (q) of approximately 0.45. A small multifactorial component (H = 0.29) acting in conjunction with a major recessive gene (q = 0.37) is not ruled out as a concomitant causative factor.

Genetic effect on apgar score

Intraclass correlation coefficients for one- and five-min Apgar scores of 604 twin pairs born at a southeastern Brazilian hospital were calculated, after adjusting these scores for gestational age and sex. The data support a genetic hypothesis only for 1-min Apgar score, probably because it is less affected by the environment than 4 min later, after the newborns have been under the care of a neonatology team. First-born twins exhibited, on average, better clinical conditions than second-born twins. The former showed a significantly lower proportion of Apgar scores under seven than second-born twins, both at 1 min (17.5 per cent vs. 29.8 per cent) and at 5 min (7.2 per cent vs. 11.9 per cent). The proportion of children born with "good" Apgar scores was significantly smaller among twins than among 1,522 singletons born at the same hospital. Among the latter, 1- and 5-min Apgar scores under seven were exhibited by 9.2 per cent and 3.4 per cent newborns, respectively.

Birth weight of twins: 1. The fetal growth patterns of twins and singletons

As distribuiçöes dos pesos de recém-nascidos de partos gemelares e únicos em três maternidades do sudeste brasileiro foram comparadas, depois do ajustamento desses pesos à idade gestacional, seus termos quadrático e cúbico, sexo e tipo de gestaçäo e as interaçöes dessas variáveis. O padräo da taxa de crescimento fetal dos gêmeos em comparaçäo ao dos recém-nascidos de parto único é retardado, independentemente do nível sócio-econômico da populaçäo examinada, mas a idade gestacional em que começa esse atraso parece estar correlacionada ao nível econômico das mäes. Em todos os casos, depois de 28 semanas de gestaçäo, o crescimento dos fetos femininos mostrou-se levemente, mas consistentemente, inferior ao dos fetos masculinos.

Birth weight of twins: 2. Fetal genetic effect on birth weight

Os coeficientes de correlaçäo intraclasse foram calculados para o peso de gêmeos nascidos em três maternidades do sudeste brasileiro, depois de ajustar os logaritmos naturais desses pesos para a idade gestacional, seus termos quadrático e cúbico, sexo e interaçöes dessas variáveis. Os dados obtidos indicaram que o efeito genético fetal sobre o peso ao nascer teria a oportunidade de ser demonstrado por recém-nascidos de mäes subnutridas. A subnutriçäo, atuando como força seletiva, realçaria a existência de genótipos que determinam menor necessidade nutricional para o desenvolvimento normal.

Maternal age and Down syndrome in Southeastern Brazil

A proporçäo de pacientes independentes da idade materna estimada em 200 crianças brasileiras com síndrome de Down (59,6 por cento) foi significativamente superior à daqueles dependentes da idade das mäes (40,4 por cento). Essa última proporçäo é a menor observada na literatura pertinente e devida, basicamente, à baixa idade média materna da populaçäo geral. Em decorrência da alta correlaçäo (r=0,95) entre a proporçäo de pacientes dependentes da idade materna e a média da idade das mäes da populaçäo geral, sugere-se uma equaçäo preditiva simples para estimar a proporçäo de casos de síndrome de Down dependentes da idade materna com base na idade materna média da populaçäo geral, quando näo existem dados confiáveis sobre a incidência dessa síndrome segundo a idade materna.

Analysis of sex distribution within families in a large Latin American sample

Uma amostra de 59.496 indivíduos latino-americanos pertencentes a 28.545 irmandades foi tomada de um grande Estudo Colaborativo de Malformaçöes Congênitas (ECLAMC). Recém-nascidos com malformaçöes congênitas e seus respectivos controles foram excluídos da amostra com a finalidade de evitar vieses associados com malformaçöes. Alguns modelos estatísticos foram aplicados, admitindo-se que os efeitos de Poisson e de Markovian näo säo importantes na determinaçäo da distribuiçäo geral das irmandades na populaçäo. O modelo geral foi o binomial duplo com excesso unicaudal. Este modelo pode ser simplificado para o binomial duplo, o binomial simples com excesso unicaudal ou o binomial simples. As primeiras três distribuiçöes ajustaram-se aos dados. Os mesmos modelos foram aplicados a vários estudos realizados em diferentes países e em épocas diferentes, os quais apresentaram resultados semelhantes. O modelo mais parcimonioso que se ajustou à maioria dos conjuntos de dados foi o binomial duplo, sugerindo que cerca de 9 por cento dos casais segregam letais recessivos ligados ao X, uma vez que as duas proporçöes de segregaçäo do modelo estäo próximas da previsäo genética.

Admixture and relationships of the population of Jacobina, Bahia, Brazil.

As part of the Cornell-Bahia project on leishmaniasis, the people of Jacobina in the state of Bahia in northeastern Brazil were studied for five genetic polymorphisms: ABO blood groups, hemoglobin variants, PGM1, 6PGD, and adenylate kinase. A maximum likelihood method of calculation of frequency of genes for these traits indicates that the ancestry of the people is 45% African, 43% Portuguese, and 12% Brazilian Indian. This estimate is similar to previous estimates of admixture in the people of northeastern Brazil, except for more African and less Caucasian ancestry. Previous distance relationships, based upon physical traits only, showed the population of Jacobina to be similar to Seminole Indians of Florida and equally distant from Whites and Blacks. While not strictly comparable, the genetic and morphologic pictures of relationships are compatible and show concordance with surnames. The presence of Hemoglobin C and the frequencies of alleles of PGM1 and 6PGD in the Jacobina population are consistent with the greater importation of Africans into Brazil from Costa de Mina on the Guinea Coast than from Angola. © 1996 Wiley-Liss, Inc.

Epidemiologia genética da hanseníase e da reaçäo de Mitsuda / Genetic epidemiology of leprosy and Mitsuda reaction

Os mecanismos genéticos que podem atuar sobre a susceptibilidade ou resistência a hanseníase sao revistos, enfatizando-se que, apesar de o modelo do camundongo ser muito atraente para ser estendido ao ser humano, as particularidades dessa doença tornam difícil qualquer extrapolaçao. Vários estudos recentes baseados na distribuiçao familiar da hanseníase nao encontraram um mecanismo genético claro responsável pela hanseníase "per se", nem para os tipos polares da doença. Contudo, foi demonstrado ser a reaçao de Mitsuda um fenótipo determinado por um gene principal com um alto grau de dominância. É enfatizado que a pesquisa deveria, agora, ser dirigida para mapear o gene responsável pela variabilidade exibida pela reaçao tardia à mitsudina injetada intradermicamente.