RESUMO
This study aims to establish the current state of the IT-15 (HTT) gene in different Ecuadorian ethnic groups and patients by determining CAG triplet repeats, compared with the ethnicity of individuals. A total of 412 individuals were studied using nested polymerase chain reaction and Sanger sequencing: 75 individuals were indigenous (Kichwas), 211 mestizos, and 65 Afro-Ecuadorians. We included 31 patients who were clinically diagnosed with Huntington's disease (HD) and relatives of the affected patients (n = 30). Moreover, we correlated the presence of HD in Ecuadorian patients with 46 genetic ancestry-informative insertion-deletion polymorphic markers. We found that 77.20% had <28 CAG repetitions, 18.80% had mutable alleles, 2.27% had incomplete penetrance, and 1.70% reflected >39 repetitions. The average of CAG repetitions was 24 ± 3 for indigenous people; 28 ± 2 for mestizos; and 24 ± 3.2 repetitions for the Afro-Ecuadorians. The ancestral component showed that the main ancestry corresponded to Native Americans (0.873) and European ascendants (0.145), Africans were less represented in the evaluated population (0.018). There was a significant difference between the number of CAG repeats in mestizos and indigenous people (P < .01), suggesting that the Ecuadorian mestizo population has a risk factor for the gene mutation.
Assuntos
Etnicidade/genética , Proteína Huntingtina/genética , Doença de Huntington/genética , Adolescente , Adulto , Idoso , Demografia , Equador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Expansão das Repetições de Trinucleotídeos/genética , Adulto JovemRESUMO
Helicobacter pylori (Hp) has a worldwide distribution showing its higher prevalence of infection in developing countries. Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) are proteins that recognize pathogen-associated molecular patterns (PAMPs) and initiate an innate immune response by promoting growth and differentiation of specialized hematopoietic cells for host defense. Gastric infections led by Hp induce a Th-1 cellular immune response, regulated mainly by the expression of IFN-γ. In this retrospective case-control study, we evaluated the TLR1 1805T/G, TLR2 2029C/T, TLR4 896A/G, CD209 -336A/G and IFNGR1 -56C/T polymorphisms and their relationship with susceptibility to Hp infection. TLR1 1805T/G showed statistical differences when the control (Hp-) and infected (Hp+) groups (P = 0.041*) were compared; the TLR1 1805G allele had a protective effect towards infection (OR = 0.1; 95% CI = 0.01-0.88, P = 0.033*). Similarly, the IFNGR1 -56C/T polymorphism showed statistical differences between Hp+ and Hp- (P = 0.018*), and the IFNGR1 -56TT genotype exhibited significant risk to Hp infection (OR = 2.9, 95% CI = 1.27-6.54, P = 0.018*). In conclusion, the pro-inflammatory TLR1 1805T and IFNGR1 -56T alleles are related with susceptibility to Hp infection in Ecuadorian individuals. The presence of these polymorphisms in individuals with chronic infection increases the risk of cellular damage and diminishes the cellular immune response efficiency towards colonizing agents.
Assuntos
Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Imunidade Inata/imunologia , Polimorfismo de Nucleotídeo Único/imunologia , Receptores de Superfície Celular/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/imunologia , Equador , Frequência do Gene , Genótipo , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Receptores de Superfície Celular/genética , Receptores de Interferon/genética , Receptores de Interferon/imunologia , Estudos Retrospectivos , Receptor 1 Toll-Like/genética , Receptor 1 Toll-Like/imunologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Adulto Jovem , Receptor de Interferon gamaRESUMO
Telomeric association (TA), i.e. fusion of chromosomes by their telomeres, predisposes a cell to genetic instability. Because of this we investigated the effect of X-rays exposure and cigarette smoking on the frequency of TA in peripheral blood lymphocytes of exposed individuals, in order to determine if TA can be a chromosomal marker in populations exposed to these carcinogens and if there is an synergistic effect between both agents. We found that the exposed groups show a greater percentage of TA when compared with the control group (P<0.001). However, although the percentage of metaphases with TA in the group with combined exposure (12.6%) was greater than in the others exposed groups (P<0.05), this value was less than the sum of the two individual effects (15.1%). Our results suggest that probably there is not an additive or synergistic effect between X-rays and smoking, and that TA may be a useful cytogenetic marker for evaluating populations exposed to mutagens.
Assuntos
Fumar/efeitos adversos , Telômero/efeitos dos fármacos , Telômero/efeitos da radiação , Raios X/efeitos adversos , Adulto , Marcadores Genéticos/efeitos dos fármacos , Marcadores Genéticos/efeitos da radiação , Humanos , Metáfase/efeitos dos fármacos , Metáfase/genética , Metáfase/efeitos da radiação , Pessoa de Meia-IdadeRESUMO
There are few reports about the incidence of the DeltaF508 mutation in Latin American countries. We show the study of the DeltaF508 mutation and the seven most common "European" mutations in 10 Ecuadorian CF affecteds. The incidence of DeltaF508 mutation found was 25% and none of the other seven was detected in our population, which indicates that at least 60% of the mutations in the studied population are different from most common in Europe. Similar data have been reported in other Amerindian populations, therefore it is suggested that Cystic Fibrosis in Ecuador-and other Amerindian countries in Latin America-have a different ethiology than that of Caucasian populations.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Indígenas Sul-Americanos/genética , Deleção de Sequência , Fibrose Cística/epidemiologia , Equador/epidemiologia , Europa (Continente) , Feminino , Humanos , Incidência , MasculinoRESUMO
This study compares the frequency of telomeric associations in the peripheral blood of women suffering breast and cervix uterine cancer with a healthy control group. Two kinds of cultures were developed for each individual: with and without aphidicolin. In the normal cultures, the number of telomeric associations observed was 95.5 times higher in individuals affected by breast cancer and 41.3 times higher in those affected by cervix uterine cancer when compared to the control group (p < 0.001). In the cultures with aphidicolin, higher numbers of altered metaphases were observed in both groups as compared to the control groups (p < 0.001). Statistically significant differences (p < 0.001) could also be observed when comparing telomeric associations between the two types of cancer in both cultures. When we compared individuals affected by breast cancer in both types of cultures statistical differences were found (p < 0.05), and similar results were found in individuals affected by uterine cervix cancer (p < 0.001). The findings suggest that telomeric associations may be reflecting chromosome instability observed in cancer and that this instability behaves differently for various types of cancer.
Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma de Células Escamosas/genética , Telômero , Neoplasias do Colo do Útero/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Cariotipagem , Metáfase , Neoplasias do Colo do Útero/patologiaRESUMO
Blood samples were obtained from 80 women: Twenty of these samples were from women affected by ductal infiltrating breast carcinoma, twenty from women affected by cervix uterine cancer, and forty individuals were screened for a control group. The search for chromosome instability that is known to affect individuals with cancer was performed through chromosome analysis in nontumor cells, intending to establish frequency and different types of numerical and structural aberrations. The results, in regard to spontaneous and aphidicolin induced chromosome aberrations, showed a significantly greater frequency (p < 0.001) of chromosome fragility, as well as other numerical and structural aberrations in breast cancer patients when compared to the control group. Similar results were obtained from cervix uterine cancer patients with the exception of certain numerical aberrations in which no significant differences were found. This suggests the existence of a certain degree of chromosomal instability affecting individuals with both types of cancer. The increase in fragility may play an important role in the biologic behavior and progression of cancer.
Assuntos
Afidicolina/farmacologia , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma de Células Escamosas/genética , Fragilidade Cromossômica , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Aberrações Cromossômicas , Cromossomos/efeitos dos fármacos , Reparo do DNA , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Inibidores da Síntese de Ácido NucleicoRESUMO
In the present study we analyzed and followed up on the cytogenetic effects of low levels of ionizing X-radiation on hospital workers at 72 h cultures. Samples of peripheral blood were collected from 10 hospital workers exposed to 1.84 mSv/year, and from 10 non exposed individuals, who were screened simultaneously and used as controls. The chromosomes were prepared using standard techniques. After 12 months, we undertook a second evaluation, this time with exposure to the same workers of 1.67 mSv/year. We observed 100 metaphases per subject, and there was a high percentage of altered metaphases (29.2% in the first sample and 26% in the second samples) The chromosome analysis in the second mitotic division, show aberrations such as gaps, breaks and acentric fragments, as well as other alterations such as dicentrics and rings, as well as chromosome variants (double minutes) in the exposed workers vs. the controls, and the difference was statistically highly significant (p < 0.001). There is no statistically significant difference between the first sample of exposed workers with the second one (p > 0.05). The findings in this study are interesting, because the workers were exposed to doses well below the accepted standards for exposure to radiations. Because of these unusual findings, our results could have potentially major consequences on our views on standards of exposure to radiation.