Navegando por Palavras-chave "Haplotypes"
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- ItemSomente MetadadadosAssociation of APOA1 and APOA5 polymorphisms and haplotypes with lipid parameters in a Brazilian elderly cohort(Funpec-editora, 2013-01-01) Furuya, Tatiane Katsue [UNIFESP]; Chen, Elizabeth Suchi [UNIFESP]; Ota, Vanessa Kiyomi [UNIFESP]; Mazzotti, Diego Robles [UNIFESP]; Ramos, Luiz Roberto [UNIFESP]; Cendoroglo, Maysa Seabra [UNIFESP]; Araujo, Lara Miguel Quirino [UNIFESP]; Burbano, Rommel Rodríguez [UNIFESP]; Smith, Marilia de Arruda Cardoso [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Apolipoproteins have an important role in lipid metabolism and transport. Polymorphisms in the APOA1/C3/A4/A5 gene cluster have been associated with lipid alterations and cardiovascular diseases. We investigated APOA1 XmnI, APOA5 S19W, and APOA5 -1131T>C polymorphisms in 377 individuals from a cohort of a longitudinal Brazilian elderly study. Allele frequencies, genotype distribution, and association with major morbidities as well as with lipids, creatinine, albumin, urea, glycated hemoglobin, and fasting glucose serum levels were investigated. Linkage disequilibrium and haplotype associations were also analyzed. This is the first time that haplotypes involving these polymorphisms were evaluated. Genotyping was performed by PCR-RFLP. Minor allele frequencies were 0.119, 0.071, and 0.158 for XmnI, S19W, and -1131T>C polymorphisms, respectively. We found a significant association of the -1131C allele with low LDL-C levels. We also observed that XmnI and S19W polymorphisms were in linkage disequilibrium. the C/G haplotype, which is composed of the wild-type allele of XmnI and the minor allele of S19W, was associated with high total cholesterol serum levels in this elderly population. We conclude that the -1131T>C polymorphism and the C/G haplotype, including XmnI and S19W polymorphisms, are associated with alterations in lipid levels and may be risk factors for cardiovascular disease in the Brazilian elderly.
- ItemAcesso aberto (Open Access)Association of interleukin 1 beta polymorphisms and haplotypes with Alzheimer's disease(Elsevier B.V., 2012-06-15) Payão, Spencer Luiz Marques [UNIFESP]; Gonçalves, Gisela Moraes; Lábio, Roger Willian de; Horiguchi, Lie; Mizumoto, Igor; Rasmussen, Lucas Trevizani [UNIFESP]; Pinhel, Marcela Augusta de Souza; Souza, Dorotéia Rossi Silva; Bechara, Marcelo Dib; Chen, Elizabeth Suchi [UNIFESP]; Mazzotti, Diego Robles [UNIFESP]; Bertolucci, Paulo Henrique Ferreira [UNIFESP]; Smith, Marilia de Arruda Cardoso [UNIFESP]; USC; Universidade Federal de São Paulo (UNIFESP); Fac Med Marilia FAMEMA; Fac Med Sao Jose do Rio Preto; Univ Marilia UNIMAROur study aimed to associate IL-1 beta and IL-1RN polyrnorphisms with AD disease in comparison with elderly control group from São Paulo - Brazil. We genotyped 199 Alzheimer's disease (AD) patients, 165 elderly control and 122 young control samples, concerning VNTR (IL-1RN) and -511C>T and -31T>C (IL-1 beta) polymorphisms. Our findings revealed that -511C/-31T/2-repetitions VNTR haplotype had a protective effect for AD when compared to EC (p=0.005), whereas -511C/-31C/1-repetition VNTR haplotype was associated as a risk factor for AD (p=0.021). Taken together, we may suggest that there is a relevant role of IL-1 genes cluster in AD pathogenesis in this Brazilian population. (c) 2012 Elsevier B.V. All rights reserved.
- ItemAcesso aberto (Open Access)Clinical, hematological, and molecular characterization of sickle cell anemia pediatric patients from two different cities in Brazil(Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz, 2005-08-01) Lyra, Isa Menezes; Gonçalves, Marilda Souza; Braga, Josefina Aparecida Pellegrini [UNIFESP]; Gesteira, Maria de Fátima; Carvalho, Maria Helena; Saad, Sara Teresinha Olalla; Figueiredo, Maria Stella [UNIFESP]; Costa, Fernando Ferreira; Fundação Hematologia e Hemoterapia da Bahia; Universidade Federal da Bahia; Fundação Oswaldo Cruz Centro de Pesquisa Gonçalo Moniz; Universidade Federal da Bahia Faculdade de Farmácia; Universidade Federal de São Paulo (UNIFESP); Universidade Estadual de Campinas (UNICAMP)This study focused on clinical, hematological, and molecular aspects of sickle cell anemia pediatric patients from two different cites in Brazil. Seventy-one patients from São Paulo and Salvador, aged 3 to 18 years, were evaluated. Hematological analyses, betaS globin gene haplotypes, and alpha2 3.7kb-thalassemia were performed. Numbers of hospitalizations due to vaso-occlusive crises, infections, stroke, and cholelithiasis were investigated. São Paulo had more hospitalizations from vaso-occlusion, cholelithiasis, and stroke than Salvador. The Ben/CAR genotype predominated in both cities. alpha2 3.7kb-thalassemia had a frequency of 28.2% in Salvador, mostly with Ben/CAR genotype (45.0%), while São Paulo had 22.5% with similar frequencies of the Ben/ CAR and CAR/CAR genotypes. Sickle cell anemia patients from São Paulo also had more episodes of stroke, which was observed among CAR/CAR, atypical, and BEN/CAR haplotypes. In Salvador stroke was only observed in the Ben/CAR genotype. Cholelithiasis had similar frequencies in the two cities. These data suggest a milder phenotype among patients in Salvador, possibly due to genetic, environmental, and socioeconomic factors. Further studies are needed to elucidate modulating factors and phenotype association.
- ItemAcesso aberto (Open Access)Haplótipos do gene Beta globina e alfa-talassemia em crianças com anemia falciforme.(Universidade Federal de São Paulo (UNIFESP), 2011-04-27) Camilo-Araújo, Roberta Faria [UNIFESP]; Amancio, Olga Maria Silverio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)A anemia falciforme e geneticamente determinada pela homozigose (SS) da hemoglobina S, em consequencia da mutacao do gene ƒÀ-globina, no sexto codon da cadeia ƒÀ no cromossomo 11 (ƒÀ6glu-val). E a doenca hematologica mais prevalente no Brasil. Os haplotipos ƒÀs estao associados com o nivel de gravidade da anemia falciforme. A prevalencia dos haplotipos ƒÀs-globina e sua relacao com os valores hematologicos e com as manifestacoes clinicas foi determinada em 122 criancas SS, de tres a 71 meses de idade. O DNA (Acido Desoxirribonucleico) foi extraido dos leucocitos, por meio de sangue perferico e a determinacao dos haplotipos foi realizada por PCR-RFLP (Reacao em Cadeia de Polimerase e Polimorfismo do Tamanho do Fragmento de Restricao). A prevalencia dos haplotipos segundo o genotipo foi de 43 (35,2%) CAR/BEN, 41 (33,6%) CAR/CAR, 25 (20,5%) RAR/ATP e 13 (10,7%) BEN/BEN. Dos 25 cromossomos RARO/ATP estao incluidos 1 (0,8%) SEN/CAR, 1 (0,8%) SAUDI/CAR, 1 (0,8%) SAUDI/BEN, 9 (7,4%) CAR/ATP, 8 (6,6%) BEN/ATP e 5 (4,1%) ATP/ATP. Na populacao estudada, o haplotipo CAR foi o mais frequente, seguido do haplotipo BEN. Ha associacao significante dos haplotipos somente com os valores de hemoglobina e volume corpuscular medio. Os haplotipos ƒÀs nao influenciam as caracteristicas clinicas das criancas portadoras de anemia falciforme, embora tenha sido observado valor menor de hemoglobina fetal no haplotipo CAR, nao ha relacao com o nivel de gravidade.
- ItemSomente MetadadadosHaplotypes of TAFI gene and the risk of cerebral venous thrombosis - a case-control study(Elsevier B.V., 2014-01-01) Orikaza, Cristina M. [UNIFESP]; Morelli, Vania M. [UNIFESP]; Matos, Marinez Farana [UNIFESP]; Lourenco, Dayse M. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: Cerebral venous thrombosis (CVT) is an uncommon disease with some differences compared to other-site thrombosis, including a higher frequency in young people, female sex and oral contraceptive users. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a regulator of fibrinolysis, whose levels are genetically controlled and its increase is associated to thrombosis. Our objective was to investigate in a case-control study the association between CVT and TAFI single nucleotide polymorphisms (SNPs) and its haplotypes in comparison to other-site venous thrombosis and controls.Materials and Methods: Seventy two patients with CVT were compared to 143 individuals with no history of thromboembolic events (control group) and to 128 patients with deep vein thrombosis in the limbs and/or pulmonary embolism(venous thromboembolism-VTE group). SNPs were genotyped by restriction fragment length polymorphism or allele-specific PCR for F2 20210G > A, F5 1691G > A, TAFI (-1053C > T, -438G > A, 505G > A, 1040C > T and + 1542C > G).Results: the GTC haplotype for TAFI 505G > A/1040C > T/+ 1542C > G SNPs was associated with an increased risk of CVT compared to controls [odds ratio (OR) 2.67, 95% confidence interval (CI): 1.13 - 6.34) and VTE group (OR 2.51, 95%CI: 1.07 - 8.06). the CVT risk became even more pronounced when evaluating unprovoked or hormone-related thrombosis cases: CVT compared to controls (OR 3.24, 95%CI: 1.19 - 8.82) and VTE group (OR 4.32, 95%CI: 1.27 - 14.63).Conclusions: Our data indicate that the GTC haplotype for TAFI 505G > A/1040C > T/+ 1542C > G SNPs increased the risk of CVT in comparison to controls and VTE cases. Further studies are required to confirm our findings. (C) 2013 Elsevier B.V. All rights reserved.
- ItemAcesso aberto (Open Access)Molecular analysis and association with clinical and laboratory manifestations in children with sickle cell anemia(Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular, 2014-10-01) Camilo-Araújo, Roberta Faria; Amancio, Olga Maria Silverio [UNIFESP]; Figueiredo, Maria Stella [UNIFESP]; Cabanãs-Pedro, Ana Carolina; Braga, Josefina Aparecida Pellegrini [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objectives: To analyze the frequency of βS-globin haplotypes and alpha-thalassemia, and their influence on clinical manifestations and the hematological profile of children with sickle cell anemia.Method: The frequency of βS-globin haplotypes and alpha-thalassemia and any association with clinical and laboratorial manifestations were determined in 117 sickle cell anemia children aged 3–71 months. The confirmation of hemoglobin SS and determination of the haplotypes were achieved by polymerase chain reaction-restriction fragment length polymorphism, and alpha-thalassemia genotyping was by multiplex polymerase chain reaction (single-tube multiplex-polymerase chain reaction).Results: The genotype distribution of haplotypes was 43 (36.7%) Central African Republic/Benin, 41 (35.0%) Central African Republic/Central African Republic, 20 (17.0%) Rare/atypical, and 13 (11.1%) Benin/Benin. The frequency of the α3.7 deletion was 1.71% as homozygous (−α3.7/−α3.7) and 11.9% as heterozygous (−α3.7/αα). The only significant association in respect to haplotypes was related to the mean corpuscular volume. The presence of alpha-thalassemia was significantly associated to decreases in mean corpuscular volume, mean corpuscular hemoglobin and reticulocyte count and to an increase in the red blood cell count. There were no significant associations of βS-globin haplotypes and alpha-thalassemia with clinical manifestations.Conclusions: In the study population, the frequency of alpha-thalassemia was similar to published data in Brazil with the Central African Republic haplotype being the most common, followed by the Benin haplotype. βS-globin haplotypes and interaction between alpha-thalassemia and sickle cell anemia did not influence fetal hemoglobin concentrations or the number of clinical manifestations.
- ItemSomente MetadadadosSplicing alternativo e polimorfismo gênico de moléculas do sistema imune(Universidade Federal de São Paulo (UNIFESP), 2006) Smirnova, Anna [UNIFESP]; Gerbase-Lima, Maria [UNIFESP]Muitos genes do genoma humano apresentam variações na sequência de DNA (polimorfismos) e também variações no splicing de mRNA (variantes de splicing, VS). A expressão de VS pode ser regulada dependendo do tipo e do estado de ativação celular, e também ser influenciada por polimorfismos. Os objetivos desta tese foram: (1) realizar busca de VS de 10 genes imunorregulatórios (TC/RG1, L TA, L TB, OX40, OX40L, BAFF, APR/L, BAFF-R, BCMA, e TACI) em células mononucleares do sangue periférico ativadas e não ativadas; (2) caracterizar polimorfismos de genes que se mostrassem interessantes em relação a VS; (3) estudar a expressão das VS dos genes selecionados em relação aos polimorfismos deste gene, ativação e tipo de linfócitos. Métodos: Novas VS foram identificadas por busca no banco de dados de ESTs e screening por RT-PCR (reverse-transcriptase polymerase chain reaction). A sua expressão foi quantificada por RT-PCR semi-quantitativo ou em tempo real. Os polimorfismos foram caracterizados utilizando enzimas de restrição e sequenciamento. Resultados: (1) identificamos sete novas VS do gene L TA, duas de BAFF e quatro de BCMA em células mononucleares de sangue periférico; todas elas podem codificar isoformas diferentes de proteína, a maioria truncadas; (2) verificamos que a expressão das VS do L TA é regulada diferencialmente em linfócitos ativados; (3) observamos que as VS do BAFF se expressam em baixos níveis em todos os tipos de células estudados e, as do BCMA, somente em células CD19+; (4) elaboramos uma nova estratégia para definição de haplótipos e provamos sua eficiência em relação aos haplótipos do gene L TA, em 102 indivíduos; (5) observamos expressão diferente de alelos do L TA em células de indivíduos heterozigotos, sem haver diferença na expressão entre indivíduos homozigotos. Conclusões: Apesar de haver dados abundantes no banco de ESTs, a busca experimental de novas VS é necessária. No exemplo do L TA, sugerimos que mesmo VS com ORF truncado e de baixa expressão podem ter importância funcional, pois são reguladas diferencialmente durante ativação de linfócitos. A nova estratégia de detecção de haplótipos, proposta neste estudo, é rápida e eficiente e pode ser aplicada para vários genes, principalmente para os quais em que a detecção, por RFLP, de pelo menos um polimorfismo já tenha sido padronizada. O estudo de expressão do LTA em relação aos polimorfismos indica a existência de um mecanismo de regulação de expressão dos alelos que atua somente quando os dois alelos estão presentes no mesmo indivíduo.