Navegando por Assunto "Polimorfismo genético"

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Allele frequency distributions of six hypervariable loci (D1S80, APOB, D4S43, vW1, F13A and DYS19) in two African-Brazilian communities from the Amazon region
(2003) VALLINOTO, Izaura Maria Vieira Cayres; VALLINOTO, Antonio Carlos Rosário; VALENTE, Cristina Maria Duarte; GUERREIRO, João Farias
The allele frequency distributions of three VNTR (D1S80, APOB and D4S43) and three STR (vW1, F13A1 and DYS19) loci were investigated in two Afro-Brazilian populations from the Amazon: Curiau and Pacoval. Exact tests for population differentiation revealed significant differences in allele frequency between populations only for the D1S80 and APOB loci. A statistically significant deviation from the Hardy-Weinberg equilibrium was observed only in the D1S80 locus of the Pacoval sample. A neighbor-joining tree was constructed based on DA genetic distances of allele frequencies in four Afro-Brazilian populations from the Amazon (Pacoval, Curiau, Trombetas, and Cametá), along with those from Congo, Cameroon, Brazilian Amerindians, and Europeans. This analysis revealed the usefulness of these Amp-FLPs for population studies - African and African-derived populations were closely grouped, and clearly separated from Amerindians and Europeans. Estimates of admixture components based on the gene identity method revealed the prevalence of the African component in both populations studied, amounting to 51% in Pacoval, and to 43% in Curiau. The Amerindian component was also important in both populations (37% in Pacoval, and 24% in Curiau). The European component reached 33% in Curiau.
Acesso aberto (Open Access)
Análise de polimorfismo na região promotora do gene da Interleucina 18 (-137 G/C e -607 C/A) em pacientes portadores do vírus da hepatite C de Belém, Pará
(Universidade Federal do Pará, 2012-03-23) SANTOS, Kemper Nunes dos; MARTINS, Luisa Caricio; http://lattes.cnpq.br/1799493244439769
Since its discovery in 1989, the hepatitis C virus (HCV) has been recognized as a major cause of chronic liver disease worldwide. Considered a public health problem worldwide involving between 170 to 350 million people infected. Host genetic factors have been implicated in the persistence of HCV infection. Studies suggest that two single nucleotide polymorphisms at position -607 C/A (rs1946518) and -137 G/C (rs187238) in the region of the gene IL-18 and have been found associated with the transcriptional promoter activity of IL -18, and potentially of IFN-γ, being associated with delayed viral clearance and persistence of the disease. We conducted a cross-sectional analytical study of the city of Belém-PA in 152 blood samples from patients infected with HCV and 188 uninfected controls. The samples were subjected to RT-PCR (Reverse Transcriptase - PCR) for detection of viral RNA and, subsequently, the PCR-RFLP (Restriction Fragment Length Polymorphism) to evaluate the polymorphism in the promoter region of IL-18 gene at positions -137 G/C and -607 C/A. The results showed no significant difference for IL-18 polymorphisms between patients and control group. But showed a significant difference for homozygous genotypes G/G (39.1%) at position -137 (OR = 3.00, CI [95%] = 1.24 – 7.22, p = 0.02), and A/A (21.7 %), position -607 (OR = 3.62, CI [95%] = 1.25 – 10.45, p = 0.03) among women than men (22.6% and 7.6%). The results showed evidence that among women, the presence of the polymorphism homozygous A/A (-607) acts as a protective factor against HCV infection, genotype as the A/A (-607) have been linked in some studies with liver disease and mild viral clearance.
Acesso aberto (Open Access)
Análise de variações genômicas em genes da região cromossômica 22q11.2 em pacientes esquizofrênicos do Estado do Pará
(Universidade Federal do Pará, 2015-08-29) MORAES, Leopoldo Silva de; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099
The COMT Val158Met and ZDHHC8 rs175174 polymorphisms have received increased attention in the molecular study of schizophrenia not only because they are localised to the main susceptibility locus of the disease, 22q11, but also because they are related to the dopaminergic status of the prefrontal cortex and the activity of several neuronal proteins, respectively. To evaluate the influence of the polymorphic genotypes on schizophrenia, we used real-time PCR to genotype 130 patients and 175 controls in a population from the North Region of Brazil. Our results indicated an absence of association between both polymorphisms and the likelihood of schizophrenia in the population studied. However, when categorised by gender, we found a dichotomous association between the Met/Met genotype of the COMT Val158Met polymorphism and susceptibility to schizophrenia, conferring a higher probability of disease in men (OR = 10.76; CI 95% = 2.09–55.34; p = 0.004) than in women (OR = 0.23; CI 95% = 0.07–0.69; p =0.009). Moreover, the variance analysis showed an association of the genotypes Val/Met (COMT Val158Met) and GG (ZDHHC8 rs175174) with higher average age at onset of schizophrenia. Our study supports the hypothesis of a gender-dependent association of the COMT Val158Met polymorphism with schizophrenia, in addition to suggesting an influence of both polymorphisms studied on the age at disease onset.
Acesso aberto (Open Access)
Análise genômica comparativa e os polimorfismos nos genes TNFA, IFNG IL6 e IL10 associados à expressão de citocinas na infecção por Plasmodium vivax no município do Itaituba, Estado do Pará
(Universidade Federal do Pará, 2018-07-19) PIMENTA, Tamirys Simão; MACHADO, Ricardo Luiz Dantas; http://lattes.cnpq.br/0307356330748427; OLIVEIRA, Edivaldo Herculano Correa de; http://lattes.cnpq.br/0094007714707651
In endemic areas of Asia, Oceania, Central and South America and in the horn of Africa P. vivax malaria is a major cause of morbidity with 35 million cases annually. In Brazil, the Amazon region concentrates almost all cases and infections registered countrywide, with more than three hundred thousand cases per year. Several evidences suggest that an exacerbated inflammatory response associated to density parasite is likely to aggravate the malaria symptoms. We assessed the haematological and immunological aspects, genetic alterations related to CNVs that could lead to phenotypic alterations, conferring resistance or susceptibility to malaria, as well the presence of polymorphisms in cytokine genes and their association with the infection in patients living in a gold-mining area in a gold-mining in the Brazilian Amazon Region, establishing patterns of immune response characteristic of primary malaria, recurrent malaria and endemic control. Six SNPs (TNFA-308G/A, IFNG+874T/A, IL6-174G/C, IL10-1082G/A, -819C/T, -592C/A) in four genes were determined; blood cell count was conducted on automatic analyzer; plasmatic cytokines IL-6, IL-10, TNF-α and IFN-γ were quantified by flow cytometry and density parasite was estimated by thick blood films with confirmation by nested-PCR; the CNV was estimated by aCGH and association between copy number and phenotypes (parasite load, mean number of clinical infections of malaria and gender) was assessed. The statistical analyzes were performed by Graph-pad prism 6.0 and Bioestat 5.0. No significant association was found between SNPs and malaria infection; cytokine levels were higher in malaria group when compared to endemic control; production of IL-10 was higher in the presence of GCC/GCC haplotype; IFN-γ levels were correlated with previous malaria episodes; malaria patients showed lower platelet numbers, reduction on white blood cells count and an increased monocyte percentage; significant increase in the IL-6 and IL-10 plasmatic levels in both malaria groups; the primary malaria patients displayed the highest significant plasmatic IFN-γ levels; recurrent malaria patients displayed the highest significant plasmatic TNF-α; malaria infection demonstrated correlation between parasite density and TNF-α, IL-6 and IL-10 levels; a total of 112 amplified genes and 12 deleted genes were observed and the CNVs found did not include any gene related to receptors or vivax malaria resistance factors. There were no statistically significant correlations between the clinical and pathological data (parasite load, mean number of clinical infections of malaria and gender) and the presence of CNVs in the patients studied. This study provides additional data on Plasmodium-host immune response and describes the quantitative changes in the human genome in P. vivax infection in an endemic area of garimpo.
Acesso aberto (Open Access)
Associação de polimorfismos de biomarcadores do envelhecimento (TP53, MDM2, UCP2, HLA-G, IL-1a, IL-4 e NFkB1) com a capacidade funcional de idosos
(Universidade Federal do Pará, 2016-05-30) PEREIRA, Esdras Edgar Batista; SANTOS, Sidney Emanuel Batista dos; http://lattes.cnpq.br/9809924843125163; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137
INTRODUCTION: The functional capacity and overall functionality of the elderly is defined as the capacity to manage their lives or take care of yourself, which is influenced by the degree of autonomy and independence of the individual. In search of understanding of the mechanisms involved in healthy aging and maintenance of functional independence, several studies try to identify candidate genes that may establish the association of genotype with phenotype studied physical fitness and the decline and loss of independence in adulthood. OBJECTIVE: The objective of this study was to investigate the possible association between the variability of polymorphisms on biomarkers of aging (TP53, MDM2, UCP2, HLA-G, IL-1a, IL-4 and NFkB1) with the functional capacity of the elderly. MATERIAL AND METHODS: This is a comparative analytical cross-sectional study, developed from the clinical and functional evaluation and analysis of polymorphisms on biomarkers of aging. The clinical and functional analysis included an assessment of functional capabilities: basic activity of daily living (ABVD), instrumental activities of daily living (AIVD), advanced activities of daily living (AAVD) and functional status (PS-ECOG) functional systems: cognition (MEEM), humor (GDS-15), mobility (TUG) and risk of falls (TT), Nutritional Status (MAN) and Sarcopenia risk (PP). Eight polymorphisms were included (two TP53, MDM2, UCP2, HLA-G, IL-1a, IL-4 and NFkB1) were genotyped by a multiplex PCR reaction followed by capillary electrophoresis. Analysis of PCR amplicons was performed by electrophoresis using the ABI Prism sequencer 3130 and GeneMapper ID v.3.2 software. RESULTS: A total of 228 elderly, mostly women (62%), with about 70 years old on average, with an average comorbidity index of 4.48 (± 2.44) points, sedentary (53%), with a history smoking (58%) and possessing a predominantly European ancestry. It was found that polymorphisms of the TP53 gene, UCP2, HLA-G, IL-1a, IL-4 and NFkB1 significant differences in functional variables between genotypes. The variables that most differed between genotypes were functional status (PS-ECOG), mobility (TUG), risk of falls (TT) and the risk of sarcopenia (PP). This suggested a possible association of these polymorphisms with risk factors or protection, which in most cases were not significant. The NFkB1 gene polymorphism (rs28362491) was the only biomarkers that demonstrated significant association results. The II genotype of this polymorphism was associated with risk of sarcopenia (PP). The elderly who had this genotype showed a three-fold greater susceptibility to muscle loss related to aging, when compared to other genotypes of the same gene. CONCLUSION: Therefore, considering the results of this study, it is believed that the use of biomarkers of aging, as a population screening test may favor the identification of elderly patients with increased susceptibility to the development of organic modifications and functional disabilities. The identification of this risk allows the targeting of strategies for prevention, control and treatment of disabilities linked to physiological or pathological aging.
Acesso aberto (Open Access)
Associação do polimorfismo do gene humano NRAMP1 na susceptibilidade/resistência para hanseníase em áreas endêmicas do estado do Pará
(Universidade Federal do Pará, 2011) SILVESTRE, Maria Perpétuo Socorro Amador; QUARESMA, Juarez Antônio Simões; http://lattes.cnpq.br/3350166863853054
Leprosy is a public health problem in the Pará state and a challeng for the Control Programs that aim strategies improvement to elimination of this disease between us. The agreement of the genetic and immunology mechanism to explain maintenc endemic disease can be one of the alternatives for problem resolution. The human gene for natural resistance associated macrophage protein – NRAMP1 is expressed in macrophages and seems to be involved with influence cellular immune responses to mycobacterium leprae infection. We evaluated the polymorphism association of this gene as reported by Buu et al (1995) with leprosy “per se” and clinical forms according to the anti-PGL-1 levels in the population studied. A total of 122 leprosy patients and 110 individual healthy coming from endemic municipalities in Para were genotyped for the polymorphism of NRAMP1. Association was found with leprosy “per se” (p=0.0087) and 3’ untranslated region with insertion/deletion of four base pairs was significantly associated with multibacillary (p=0.025) compared to contacts not cosanguineos. Heterozygotes and haplotypes with four base pairs deletion were more frequent among multibacillary than paucibacillary. The NRAMP1 gene haplotypes seem to have important influence on leprosy clinical presentation also revealed by Mycobacterium leprae anti-PGL-1 positively.
Acesso aberto (Open Access)
Avaliação da toxicidade e correlação com polimorfismos no gene de reparo X-RCC1 em pacientes com neoplasias do trato gastrointestinal submetidos a radio e quimioterapia
(Universidade Federal do Pará, 2015-12-18) SOUZA, Paulo Gustavo Cavalcanti de; ASSUMPÇÃO, Paulo Pimentel de; http://lattes.cnpq.br/7323606327039876; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137
The intestine tract neoplasms consist in an important problem of Brazil’s health as consequence of its incidence and mortality. Radiotherapy plays a fundamental work as part of gastric and rectal cancer treatment. The vastly background in radiobiology and the recently advances in the comprehension of molecular mechanisms involved in the behaviour of tumour cells and the normal tissues to ionizing radiation has been demonstrating the importance of repair DNA genes. The gene XRCC-1 plays an important work repairing ionizing lesions, working in the answers of single strand break through repairing by base excision. XRCC-1 base polymorphisms can influence the answer of radiotherapy’s answer, in the same way the toxicity showed on them. In the present study we analysed the toxicity of gastric and rectal cancer patients submitted to radiation treatment and chemotherapy and its relation with the occurrence of specifics polymorphisms of XRCC-1 GENE, C194T (rs1799782) and INDEL 4 bp GGCC (rs3213239). Our data showed a general toxicity rate of 64,5 %, but only 24,5 % were grade 3 or 4. The specific toxicity grade 3 or 4 rate were 16,3 % diarrhea, 6 % dermatitis and 6 % nausea. We did not find and correlation between the polymorphisms C194T (rs1799782) and INDEL (rs1799782) and the rate of toxicity found, except when we evaluated patients with gastric and rectal cancer separately. In the latter group, the allele T of C194T was associated with a higher incidence of nausea, with a 10,5 fold risk and a p value of 0,03. Although this positive correlation, we believe that the number of patients in our study was insufficient to a more accurate correlation between toxicity and polymorphisms.
Acesso aberto (Open Access)
Avaliação de polimorfismos de genes metabolizadores de xenobióticos em pacientes com fissura labiopalatina atendidos no Estado do Pará
(Universidade Federal do Pará, 2013) KHAYAT, Bruna Cláudia Meireles; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099
Orofacial cleft palate or lip is one of the most common birth defects and several existing studies that relate to multifactorial causes malformation. Among the various environmental causes are the ethyl and maternal smoking habits, as well as the use of pesticides. The response of human embryo teratogenic agents is well known. However, it is known that different organisms metabolize differently the same chemical component, this is due to intrinsic genetic characteristics related to different enzymatic runs. Such differences can be investigated from the analysis of polymorphisms in genes related to metabolism of these xenobiotics, which may well be related to etiogênese palatine cleft lip. The objective of our study was to analyze polymorphisms in seven genes, PON1 ( rs662), PON1 ( rs854560 ), MTHFD1, CYP2E1, EPHX1, ABCB1, AHR, where a correlative analysis with environmental factors such as exposure to pesticides was performed in order to assess whether there is influence of different polymorphic variants and environmental interactions in such etiogênese of cleft Lip and Palate. The total number of samples analyzed were 166 subjects, 83 patients affected by cleft, with an average age of 7 years (SD 5 years) and 83 mothers of the same. In our samples, the males was 64 % of the total affected. A plug for the collection of epidemiological data was developed for the study, the biological material collected for analysis was blood. Statistical analysis was performed using the BioStat 5.3, SPSS 12.0 software and plink 1:07. Our result is four different analyzes for each polymorphism. Initially, we observed differences between genotypic frequencies found in affected and mothers of these populations and those of healthy individuals. This aimed to find differences among genotypes that may justify the genesis of FLP, after exposure of mothers and intrauterinamente of the children to pesticides. Secondly, we looked at whether there were differences between the affected and maternal genotypes, which could represent significant differences between these two groups of individuals (as the mothers, regardless of exposure to pesticides could have FLP if the genotype was of high importance) and which may be related to the FLP. In a third analysis, we observed that the genotypes found in individuals with FLP, are related to the reported pesticide exposure as an etiological factor of these malformations. Ultimately, we aim, through regression analysis to determine whether the genotypic characteristics of these targets of study, may have influenced the phenotype of the type of cleft, lip only be either palate or cleft lip. The distribution of types of cracks between affected was 12% only for chapped lips, only 19% to 69% palate and the cracks in our sample group reached the lip and palate.
Acesso aberto (Open Access)
Biochemical polymorphisms and genetic relationships between Brazilian and foreign breeds of pigs reared in Brazil
(1999-06) TAGLIARO, Claudia Helena; FRANCO, Maria Helena Lartigau Pereira; SCHNEIDER, Maria Paula Cruz; BRITO, Benito Guimarães de; BARBOSA, Antonio Stockler; Centro de Ciências Rurais
The genetic variability of 14 protein systems encoded by 15 structural loci was investigated in blood samples of Piau and Caruncho pig breeds. The results were compared with those obtained previously for samples of Landrace, Large White, Duroc and Mouro. The degree of genetic variability obtained for Piau (He=0.114) was similar to that estimated for other breeds reared in Brazil (Landrace, He=0.116; Large White, He=0.119; Duroc, 0.095; Mouro, He= 0.130). Caruncho showed the lowest variability (He= 0.056). The gene frequencies at the polymorphic loci were used to evaluate the usefulness of these systems for paternity testing and the combined probabilities of paternity exclusion were estimated at 58% for the Piau and 36% for the Caruncho breed. Analysis of genetic distances revealed that the greatest similarity observed was between Piau and Landrace (D=0.042). Caruncho showed the greatest divergence among all breeds compared and the distances between this breed and others range from 0.107 (with Landrace) to 0.176 (with Duroc). The tree constructed by UPGMA and Rogers Distance gave a topology in which Piau and Mouro joined with the European breeds (Landrace and Large White) whereas Caruncho was separated from all the other breeds. The results of the analysis of the Caruncho samples should be interpreted with caution since the number of animals studied was small.
Acesso aberto (Open Access)
Determination of strains of Helicobacter pylori and of polymorphism in the interleukin-8 gene in patients with stomach cancer
(2011) VINAGRE, Ruth Maria Dias Ferreira; CORVELO, Tereza Cristina de Oliveira; ARNAUD, Vanda Catão; LEITE, Ana Claudia Klautau; BARILE, Katarine Antonia dos Santos; MARTINS, Luisa Caricio
CONTEXT: Gastric neoplasia is the second most common cause of death by cancer in the world and H. pylori is classified as a type I human carcinogen by the World Health Organization. However, despite the high prevalence of infection by H. pylori around the world, less than 3% of individuals carrying the bacteria develop gastric neoplasias. Such a fact indicates that evolution towards malignancy may be associated with bacterial factors in the host and the environment. OBJECTIVES: To investigate the association between polymorphism in the region promoting the IL-8 (-251) gene and the H. pylori genotype, based on the vacA alleles and the presence of the cagA gene, using clinical and histopathological data. METHODS: In a prospective study, a total of 102 patients with stomach cancer and 103 healthy volunteers were analysed. Polymorphism in interleukin 8 (-251) was determined by the PCR-restriction fragment length polymorphism reaction and sequencing. PCR was used for genotyping the vacA alleles and the cagA in the bacterial strains PCR. Gastric biopsies were histologically assessed. RESULTS: The H. pylori serology was positive for 101 (99%) of all patients analysed, and 98 (97%) of them were colonized by only one strain. In patients with monoinfection, 82 (84%) of the bacterial strains observed had the s1b/m1 genotype. The cagA gene was detected in 74 (73%) of patients infected by H. pylori. The presence of the cagA gene was demonstrated as associated with the presence of the s1b/m1 genotype of the vacA gene (P = 0.002). As for polymorphism in the interleukin 8 (-251) gene we observed that the AA (P = 0.026) and AT (P = 0.005) genotypes were most frequent in the group of patients with gastric adenocarcinoma. By comparing the different types of isolated bacterial strains with the interleukin -8 (-251) and the histopathological data we observed that carriers of the A allele (AT and AA) infected by virulent strains (m1s1 cagA+) demonstrated a greater risk of presenting a degree of inflammation (OR = 24.75 CI 95% 2.29-267.20 P = 0.004) and increased neutrophilic activity (OR = 28.71 CI 95% 2.62-314 P = 0.002) in the gastric mucosa. CONCLUSION: Our results demonstrate that the interaction between polymorphism in the interleukin -8 (-251) gene, particularly with carriers of the A allele and the infecting type of H. pylori strain (s1m1 cagA positive) performs an important function in development of gastric adenocarcinoma.
Acesso aberto (Open Access)
Estudo da influência do uso de agrotóxicos e de polimorfismo do gene GSTT1 na etiologia de fissuras labiopalatais em pacientes do Estado do Pará
(Universidade Federal do Pará, 2014-08-28) MARTINS, Cláudia Maria da Rocha; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099
Birth defect or congenital malformation is any anatomic, metabolic or functional abnormality, inherited by a mechanism of Mendelian transmission or caused by a new mutation, a chromosomal alteration or physical aggression by an infectious, chemical or the fetus or embryo development . Its causes may be genetic or environmental, and, most often, are multifactorial origin, through the genetic predisposition factors interact with environmental factors triggers. In Pará state, a large number of individuals affected by Oral clefts are from rural areas, mainly in the northeastern state where it is notoriously indiscriminate use of pesticides harmful to human health, many of which have high potential teratogenic. The objective of our study was to investigate the association between the polymorphism (rs4630) in the GSTT1 gene and exposure to pesticides in etiology of oral clefts and analyze the pattern of changes in speech of patients according to the type of cleft. Eight three patients with cleft palate or lip, and of both sexes, and 83 mothers of these patients, all from the state of Pará, residing in rural and capital area were analyzed. Speech therapy and analyzes were performed with the blood of these individuals, the molecular analysis was performed. Statistical analysis was performed using the statistical software SPSS v.. 12.0 and BioEstat v. 5.0. Tests included testing multiple logistic regression test x2e the Fisher exact test. Our result consists of five different molecular analyzes. We found that the presence of the C allele in the genotype of the individual can influence the metabolism of xenobiotics and increase the risk to develop oral clift.
Acesso aberto (Open Access)
Estudo da susceptibilidade à infecção pelo HIV-1 e da progressão da AIDS em associação ao polimorfismo no gene Mbl (Lectina Ligadora de Manose)
(Universidade Federal do Pará, 2004-09-12) COSTA, Marcos Rogério Menezes da; VALLINOTO, Antonio Carlos Rosário; http://lattes.cnpq.br/3099765198910740
The low serum concentration of Mannose-Binding Lectin (MBL) is associated to the presence of variant alleles Mbl-*B, Mbl-*C and Mbl-*D, and it results in an increased susceptibility to recurrent infections. The present study investigated the association between the Mbl gene polymorphism and the susceptibility to HIV-1 infection. A fragment of 349 bp from the exon 1 of the Mbl gene was amplified by PCR and then submitted to RFLP analysis using the endonucleases BanI and MboII, aiming the identification of the variant alleles. The study of 145 seropositive patients and 99 healthy controls showed the presence of alleles Mbl-*A, Mbl-*B and Mbl-*D, with frequencies of 69%, 22% and 9% among patients and 70.2%, 13.6% and 16.2% among healthy controls, respectively. The analysis of the genotype frequencies showed a high prevalence of the genotypes carriers of variant Mbl-*B among patients seropositive as compared to the healthy controls. Furthermore, the genotype B/B was six times more frequent among patients than the observed to the healthy controls (χ2=4.042; p=0.044). The mean viral load was lower in HIV-1 seropositive patient carrying the Mbl-*A allele than those carrying the variant Mbl-*B allele (5,821 copies/mL vs. 52,253 copies/mL; p= 0.05). Furthermore, patients carrying the allele Mbl-*A showed a significant reduction of the viral load (p<0.001), that was not observed among those carrying the variant Mbl-*B (p=0.999). The results suggest the importance of the Mbl gene polymorphism on the clinical evolution of the patients infected by HIV-1 and that the identification of the Mbl genetic profile, among HIV-1 infected patients, may be an important tool to monitor the evolution and the prognosis of diseases.
Acesso aberto (Open Access)
Estudo de potenciais marcadores moleculares de suscetibilidade ao câncer de pulmão
(Universidade Federal do Pará, 2015-08-27) SILVA, Francisco Anderson; SORTICA, Vinicius de Albuquerque; http://lattes.cnpq.br/2046482071071824
Lung cancer is a major public health problem, currently occupying the tenth position among the leading causes of death worldwide and the leading cause of death among cancer. The individual predisposition to developing lung cancer could be associated with genetic polymorphisms related to the inflammatory response, activation mechanisms and detoxification or carcinogens, as well as defects in the mechanisms of the DNA repair. This study aimed to investigate the influence of 13 polymorphisms of the type insertion / deletion in genes of the metabolism and biotransformation (CYP2E1, CYP19A1 and UGT1A1), control genes of the immune system and inflammatory response (IL1A and IL4), genes that regulate control of gene function of the cell cycle and immune system (MDM2 and NFKB1), DNA repair genes (TYMS and XRCC1), regulator of apoptosis gene (CASP 8), regulator of hemostasis gene (PAR1) and control gene cell cycle (TP53) as susceptibility to lung cancer. Polymorphisms were genotyped by a multiplex PCR reaction of patients with a confirmed diagnosis for lung cancer and individuals from the same population without the disease. The genetic ancestry of all individuals were estimated by a panel of ancestry informative markers. A logistic regression analysis controlling for age, gender and smoking was performed to determine the influence of polymorphisms in susceptibility to cancer. No statistically significant differences between the groups with cancer and without cancer were founded. Polymorphisms studied are not associated with susceptibility to lung cancer in the Pará population.
Acesso aberto (Open Access)
Farmacogenética do Gene TPMT na resposta A 6-Mercaptopurina, em pacientes com Leucemia Linfoblástica Aguda
(Universidade Federal do Pará, 2016-03-03) LIMA, Carlos Henrique Vasconcelos de; ASSUMPÇÃO, Paulo Pimentel de; http://lattes.cnpq.br/7323606327039876; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137
Acute Lymphoblastic Leukemia (ALL) is the most common type of cancer in children under 15 years of age. 6-mercaptopurine (6-MP) is one of the most widely used chemotherapeutic agents in the treatment of childhood ALL. Polymorphisms in thiopurine S-methyltransferase gene (TPMT) may be associated with individual variation in the response to treatment of childhood ALL, such as increased severe toxicity (grade 3 and 4). The aim of this study was to associate polymorphisms of TPMT gene: TPMT*2 (238G>C), TPMT*3A (460G>A and 719A>G), TPMT*3B (460G>A), TPMT*3C (719A>G), TPMT* 8 (644G>A) and intronic variant rs12201199 (94T>A) with the occurrence of serious toxicities in patients with ALL treated with 6-MP, in Northern Brazil. One hundred thirty-seven pediatric patients with ALL and treated at the Ophir Loyola Hospital in the state of Pará were investigated. The rs12201199 polymorphism was genotyped by real-time PCR (equipment 7500 Real-Time PCR System) and other polymorphisms were genotyped by direct sequencing using the automated sequencer ABI PRISM 3130 Genetic Analyzer (Applied Biosytems, CA, USA). The haplotypes among the studied polymorphisms were derived via maximum likelihood estimates using the program PHASE. A panel of 48 markers Ancestry Informative was used as genomic control in the sample and statistical analyses were performed using SPSS v.20.0 software (SPSS, Chicago, IL, USA). All statistical tests considered the probability (p) significant when ≤0, 05. In relation to the genomic ancestry, it was noted that the ethnic composition of ALL patients was 44% Caucasian, 22% African and 34% Amerindian. Among the reported toxicities, infectious was most prevalent (86%), followed by hematological (65%), gastrointestinal (64.8%) and central nervous system toxicity (29.9%). Allele frequency of polymorphism rs12201199 was 0.482 among the studied subjects. The most prevalent haplotype variants were TPMT*3A (7.6%), followed by TPMT*3C and TPMT*8, both 7.3%. There was no significant association between poor metabolism profiles of TPMT with none of the serious toxicities reported in the studied patients with LLA. However, our data show that there is a significant relationship between the polymorphism of TPMT gene (rs12201199) and the occurrence of severe infectious toxicity during treatment of childhood ALL. It has been observed that patients who have mutant homozygous AA genotype for this polymorphism in TPMT gene have 4.098 times higher risk of presenting severe infectious toxicity during the treatment for childhood ALL compared to those with the other genotypes. This result may be important to help predict risk of toxicity during treatment, contributing to a better individual prognosis of patients with childhood ALL.
Acesso aberto (Open Access)
Frequencies of CCR5-D32, CCR2-64I and SDF1-3'A mutations in Human Immunodeficiency Virus (HIV) seropositive subjects and seronegative individuals from the state of Pará in Brazilian Amazonia
(2005-12) CARVALHAES, Fernanda Andreza de Pinho Lott; CARDOSO, Greice de Lemos; VALLINOTO, Antonio Carlos Rosário; MACHADO, Luiz Fernando Almeida; ISHAK, Marluísa de Oliveira Guimarães; ISHAK, Ricardo; GUERREIRO, João Farias
The distribution of genetic polymorphisms of chemokine receptors CCR5-D32, CCR2-64I and chemokine (SDF1-3 A) mutations were studied in 110 Human Immunodeficiency Virus type 1 (HIV-1) seropositive individuals (seropositive group) and 139 seronegative individuals (seronegative group) from the population of the northern Brazilian city of Belém which is the capital of the state of Pará in the Brazilian Amazon. The CCR5-D32 mutation was found in the two groups at similar frequencies, i.e. 2.2% for the seronegative group and 2.7% for the seropositive group. The frequencies of the SDF1-3 A mutation were 21.0% for the seronegative group and 15.4% for the seropositive group, and the CCR2-64I allele was found at frequencies of 12.5% for the seronegative group and 5.4% for the seropositive group. Genotype distributions were consistent with Hardy-Weinberg expectations in both groups, suggesting that none of the three mutations has a detectable selective effect. Difference in the allelic and genotypic frequencies was statistically significant for the CCR2 locus, the frequency in the seronegative group being twice that found in the seropositive group. This finding may indicate a protective effect of the CCR2-64I mutation in relation to HIV transmission. However, considering that the CCR2-64I mutation has been more strongly associated with a decreased risk for progression for AIDS than to the resistance to the HIV infection, this could reflect an aspect of population structure or a Type I error.
Acesso aberto (Open Access)
Frequency of the Q192R and L55M polymorphisms of the human serum paraoxonase gene (PON1) in ten Amazonian Amerindian tribes
(2005-03) SANTOS, Ney Pereira Carneiro dos; SANTOS, Ândrea Kely Campos Ribeiro dos; SANTOS, Sidney Emanuel Batista dos
Human serum paraoxonase (PON1) is an esterase associated with high density lipoproteins (HDLs) in the plasma and may confer protection against coronary artery disease. Serum PON1 levels and activity vary widely among individuals and populations of different ethnic groups, such variations appearing to be related to two coding region polymorphisms (L55M and Q192R). Several independent studies have indicated that the polymorphism at codon 192 (the R form) is a significant risk factor for cardiovascular disease in some populations, although this association has not been confirmed in other populations. Given the possible associations of these mutations with heart diseases and the fact that little or nothing is known of their prevalence in Amerindian populations, we investigated the variability of both polymorphisms in ten Amazonian Indian tribes and compared the variation found with that of other Asian populations in which both polymorphisms have been investigated. The results show that the LR haplotype is the most frequent and the MR haplotype is absent in all Amerindians and Asian populations. We also found that South America Amerindians present the highest frequency of the PON1192*R allele (considered a significant risk factor for heart diseases in some populations) of all the Amerindian and Asian populations so far studied.
Acesso aberto (Open Access)
Genetic characterization of the population of São Luís, MA, Brazil
(2005-03) FERREIRA, Francileide Lisboa; MESQUITA, Emygdia Rosa Leal; SANTOS, Sidney Emanuel Batista dos; SANTOS, Ândrea Kely Campos Ribeiro dos
Five loci (vWA1, F13A1, D12S67, Apo-B and D1S80) were investigated by polyacrylamide gel electrophoresis followed by silver staining in a sample of 177 individuals from the population of São Luís, State of Maranhão, Brazil. A total of 70 different alleles were identified. A statistically significant deviation from the Hardy-Weinberg equilibrium was observed in a single locus (F13A1, p = 0.0075). The average heterozygosity (H) was estimated at 77.7%, the mean number of alleles per locus as 14. The PD (capacity of genotype differentiation at each locus) ranged from 88.9% (vWA1) to 96.7% (F13A1). The combined PE (power of exclusion) of these five loci was 99.8%. In terms of racial admixture (42% European, 39% Indian, and 19% African Black ancestry), São Luís presented an estimate similar to Belém, another trihybrid Amazonian population.
Acesso aberto (Open Access)
Genetic polymorphism and relationships among several swine populations of landrace, large white and duroc breeds
(1997-08) TAGLIARO, Claudia Helena; FRANCO, Maria Helena Lartigau Pereira; WEIMER, Tania Azevedo
The data of three protein polymorphisms were used to investigate the genetic relationships among the Landrace, Large White and Duroc swine breeds reared in Brazil, 12 other populations of these same breeds from various countries and a population of Belgium Landrace. The dendrogram, constructed from matrix of genetic distance coefficients, disclosed three large groups clustered by breed. Among them, the Landrace and the Large White showed in average closer resemblance (D = 0.203) than between them and Duroc (D = 0.241). It the three breeds, the smallest genetic distances were found between Brazilian and Cuban pig populations (Landrace: D = 0.060; Large White: D = 0.052; Duroc: D = 0.065), although there were not reports of pig exchanges between these two countries.
Acesso aberto (Open Access)
Genetic relationships among native americans based on beta-globin gene cluster haplotype frequencies
(2003) RIBEIRO, Rita de Cassia Mousinho; SOUSA, Gabriella Pante de; SANTOS, Eduardo José Melo dos; GUERREIRO, João Farias
The distribution of b-globin gene haplotypes was studied in 209 Amerindians from eight tribes of the Brazilian Amazon: Asurini from Xingú, Awá-Guajá, Parakanã, Urubú-Kaapór, Zoé, Kayapó (Xikrin from the Bacajá village), Katuena, and Tiriyó. Nine different haplotypes were found, two of which (n. 11 and 13) had not been previously identified in Brazilian indigenous populations. Haplotype 2 (+ - - - -) was the most common in all groups studied, with frequencies varying from 70% to 100%, followed by haplotype 6 (- + + - +), with frequencies between 7% and 18%. The frequency distribution of the b-globin gene haplotypes in the eighteen Brazilian Amerindian populations studied to date is characterized by a reduced number of haplotypes (average of 3.5) and low levels of heterozygosity and intrapopulational differentiation, with a single clearly predominant haplotype in most tribes (haplotype 2). The Parakanã, Urubú-Kaapór, Tiriyó and Xavante tribes constitute exceptions, presenting at least four haplotypes with relatively high frequencies. The closest genetic relationships were observed between the Brazilian and the Colombian Amerindians (Wayuu, Kamsa and Inga), and, to a lesser extent, with the Huichol of Mexico. North-American Amerindians are more differentiated and clearly separated from all other tribes, except the Xavante, from Brazil, and the Mapuche, from Argentina. A restricted pool of ancestral haplotypes may explain the low diversity observed among most present-day Brazilian and Colombian Amerindian groups, while interethnic admixture could be the most important factor to explain the high number of haplotypes and high levels of diversity observed in some South-American and most North-American tribes.
Acesso aberto (Open Access)
HLA-Bw4-B*57 and Cw*18 alleles are associated with plasma viral load modulation in HIV-1 infected individuals in Salvador, Brazil
(2010-10) SILVA, Edinete Melo da; ACOSTA, Angelina Xavier; SANTOS, Eduardo José Melo dos; MARTINS NETTO, Eduardo; LEMAIRE, Denise Carneiro; OLIVEIRA, Adriano Silva; BARBOSA, Ana Caroline de Matos; BENDICHO, Maria Teresita; CASTRO FILHO, Bernardo Galvão; ALVES, Carlos Roberto Brites
Host genetic factors play an important role in mediating resistance to HIV-1 infection and may modify the course of infection. HLA-B alleles (Bw4 epitope; B*27 and B*57) as well as killer cell immunoglobulin-like receptors have been associated with slow progression of HIV-1 infection. OBJECTIVE: To evaluate the association between serological epitopes HLA-Bw4 and HLA-Bw6 and prognostic markers in AIDS. METHODS: 147 HIV-infected individuals in Bahia, Northeast Brazil, were genotyped for HLA class I locus. HLA class I genotyping was performed by hybridization with sequence-specific oligonucleotide probes following amplification of the corresponding HLA-A, HLA-B and HLA-C genes. Statistical analysis was performed using Fisher's exact and ANOVA tests for categorical and continuous variables, respectively. RESULTS: We detected a significant association (χ2 = 4.856; p = 0.018) between the presence of HLA-Bw4 and low levels of viremia. Eighteen out of the 147 HIV-infected individuals presented viremia <1,800 copies/mL and 129 presented viremia > 2,000 copies/mL. Ninety and four percent (17/18) of all individuals with viremia < 1,800 copies/mL carried HLA-Bw4, compared to 67.4% (87/129) of individuals with viremia > 2,000 copies/mL. Additionally, we found a significantly higher frequency of B*57 (OR = 13.94; 95% CI = 4.19-46.38; p < 0.0001) and Cw*18 (OR = 16.15; 95% CI = 3.46-75.43; p < 0.0001) alleles, favoring the group with lower viremia levels, in comparison with those with higher viral load. CONCLUSION: HLA-Bw4-B*57 and Cw*18 alleles are associated with lower level of viral load in HIV-infected Brazilian patients. These findings may help us in understanding the determinants of HIV evolution in Brazilian patients, as well as in providing important information on immune response correlates of protection for such population.