Navegando por Palavras-chave "polymorphisms"

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    ADIPOQ and adiponectin: the common ground of hyperglycemia and coronary artery disease?
    (Sociedade Brasileira de Endocrinologia e Metabologia, 2011-10-01) Oliveira, Carolina Soares Viana de [UNIFESP]; Giuffrida, Fernando M. A. [UNIFESP]; Crispim, Felipe [UNIFESP]; Saddi-rosa, Pedro [UNIFESP]; Reis, André Fernandes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to explain part of the interaction between obesity, insulin resistance, type 2 diabetes (T2DM) and coronary artery disease (CAD). Here, we illustrate the role that adiponectin and ADIPOQ variants might play in the modulation of CAD, especially in the occurrence of hyperglycemia. Recent evidence suggests that total and high molecular weight (HMW) adiponectin levels are apparent markers of better cardiovascular prognosis in patients with low risk of CAD. However, in subjects with established or high risk of CAD, these levels are associated with poorer prognosis. We also provide recent evidences relating to the genetic control of total and HMW adiponectin levels, especially evidence regarding ADIPOQ. Accumulated data suggest that both adiponectin levels and polymorphisms in the ADIPOQ gene are linked to the risk of CAD in patients with hyperglycemia, and that these associations seem to be independent from each other, even if adiponectin levels are partly dependent on ADIPOQ.
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    Association Between Interleukin 6 Gene Haplotype and Alzheimer's Disease: A Brazilian Case-Control Study
    (Ios Press, 2013-01-01) Rasmussen, Lucas [UNIFESP]; Delabio, Roger; Horiguchi, Lie; Mizumoto, Igor; Terazaki, Carlos-Renato; Mazzotti, Diego [UNIFESP]; Bertolucci, Paulo-Henrique [UNIFESP]; Pinhel, Marcela-Augusta; Souza, Doroteia; Krieger, Henrique; Kawamata, Carlos; Minett, Thais; Smith, Marilia Cardoso [UNIFESP]; Payao, Spencer-Luiz; USC; Fac Med Marilia FAMEMA; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Univ Cambridge
    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.
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    Casein kinase I epsilon (CKI epsilon) N408 allele is very rare in the Brazilian population and is not involved in susceptibility to circadian rhythm sleep disorders
    (Elsevier B.V., 2008-11-03) Castro, Rosa M. R. P. S. [UNIFESP]; Barbosa, Ana A. [UNIFESP]; Pedrazzoli, Mario [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Circadian rhythms are regulated by clock proteins through post-translational modifications. Indeed, Casein kinase I epsilon (CKI epsilon) promotes reversible phosphorylation of PER proteins, and a deficiency in this phosphorylation has been implicated in human sleep disorders. Here, we investigated the CKI epsilon S408N polymorphism in a Brazilian population sample. the N408 allele was previously described to be much less frequent in individuals with Delayed Sleep-Phase Syndrome (DSPS), than in the general Japanese population, Suggesting a protective function for the allele against the disease. We found that this polymorphism is very rare in the Brazilian population (1.37%), indicating that it has no influence on susceptibility to circadian rhythm sleep disorders. Therefore, it is necessary to account for adaptative influences in genetic background, analyzing different groups with different photoperiods, to validate the effects of this and other polymorphisms on sleep and circadian disorders. (C) 2008 Elsevier B.V. All rights reserved.
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    Cytokine gene variants and venous thrombotic risk in the BRATROS (BRAZILIAN THROMBOSIS STUDY)
    (Elsevier B.V., 2007-01-01) Pieroni, Fabiano; Lourenco, Dayse M.; Morelli, Vania M.; Maffei, Francisco H.; Zago, Marco A.; Franco, Rendrik F.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); State Univ Sao Paolo; Fleury Res Inst
    Introduction: Venous thrombosis (VT) and inflammation are two closely related entities. in the present investigation we assessed whether there is a relation between genetic modifiers of the inflammatory response and the risk of VT.Materials and methods: 420 consecutive and unrelated patients with an objective diagnosis of deep VT and 420 matched controls were investigated. the frequencies of the following gene polymorphisms were determined in all subjects: TNF-alpha-308 G/A, LT-alpha+252 A/G, IL-6-174 G/C, IL1-ra 86 bp VNTR, IL-10-1082 A/G and CD-31 125 C/G.Results: Overall odds ratio (OR) for VT related to TNF-alpha-308 G/A, LT-alpha+252 A/G, IL-6-174 G/C, Al allele (4 bp repeat) of the IL1 -ra 86 bp VNTR, IL-10-1082 A/G and CD-31 125 C/G were respectively: 1.0 (CI95: 0.8-1.5), 1.3 (095: 1.0-1.7), 1.1 (CI95: 0.9-1.5), 1.6 (CI95: 1-2.5), 1.2 (CI95: 0.8-1.7) and 0.8 (CI95: 0.6-1.1). A possible interaction between polymorphisms was observed only for the co-inheritance of the mutant alleles of the LT-alpha+252 A/G and IL-10-1082 G/A polymorphisms (OR=2; CI95: 1.1-3.8). the risk of VT conferred by factor V Leiden and FII G20210A was not substantially altered by co-inheritance with any of the cytokine gene polymorphisms.Conclusions: Cytokine gene polymorphisms here investigated did not significantly influence venous thrombotic risk. (C) 2006 Elsevier B.V. All rights reserved.
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    Frequency of polymorphisms of genes coding for HIV-1 co-receptors CCR5 and CCR2 in a Brazilian population
    (Brazilian Society of Infectious Diseases, 2003-08-01) Munerato, Patricia [UNIFESP]; Azevedo, Maria Lúcia [UNIFESP]; Sucupira, Maria Cecília Araripe [UNIFESP]; Pardini, Regina [UNIFESP]; Pinto, Gedson Humberto Novaes [UNIFESP]; Catroxo, Márcia [UNIFESP]; Souza, Inara Espinelli [UNIFESP]; Diaz, Ricardo Sobhie [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Entry of human immunodeficiency type 1 virus (HIV-1) into target cells requires both CD4and one of the chemokine receptors. Viruses predominantly use one, or occasionally both, of the major co-receptors CCR5 and CXCR4, although other receptors, including CCR2B and CCR3, function as minor co-receptors. A 32-nucleotide deletion (delta32) within the beta-chemokine receptor 5 gene (CCR5) has been described in subjects who remain uninfected despite extensive exposition to HIV-1. The heterozygous genotype delays disease progression. This allele is common among Caucasians, but has not been found in people of African or Asian ancestry. A more common transition involving a valine to isoleucine switch in transmembrane domain I of CCR2B (64I), with unknown functional consequences, was found to delay disease progression but not to reduce infection risk. As the Brazilian population consists of a mixture of several ethnic groups, we decided to examine the genotype frequency of these polymorphisms in this country. There were 11.5% CCR5 heterozygotes among the HIV-1 infected population and 12.5% among uninfected individuals, similar to data from North America and Western Europe. The prevalence of CCR2-64I homozygotes and heterozygotes was 0.06 and 15.2%, respectively, also similar to what is known for North America and Western Europe.
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    Genotype-guided warfarin therapy: current status
    (Future Medicine Ltd, 2018) Tavares, Leticia C.; Marcatto, Leiliane R.; Santos, Paulo C. J. L. [UNIFESP]
    Warfarin pharmacogenomics has been an extensively studied field in the last decades as it is focused on personalized therapy to overcome the wide interpatient warfarin response variability and decrease the risk of side effects. In this expert review, besides briefly summarizing the current knowledge about warfarin pharmacogenetics, we also present an overview of recent studies that aimed to assess the efficacy, safety and economic issues related to genotype-based dosing algorithms used to guide warfarin therapy, including randomized and controlled clinical trials, meta-analyses and cost-effectiveness studies. To date, the findings still present disparities, mostly because of standard limitations. Thus, further studies should be encouraged to try to demonstrate the benefits of the application of warfarin pharmacogenomic dosing algorithms in clinical practice.
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    The Gly482Ser polymorphism in the peroxisome proliferator-activated receptor-gamma coactivator-1 gene is associated with hypertension in type 2 diabetic men
    (Springer, 2004-11-01) Cheurfa, Nadir; Reis, André Fernandes [UNIFESP]; Dubois-Laforgue, Daniele; Bellanne-Chantelot, Christine; Timsit, José; Velho, Gilberto [UNIFESP]; Hop St Vincent de Paul; Universidade Federal de São Paulo (UNIFESP); Cochin Hosp; Hop St Antoine
    Aims/hypothesis. Peroxisome proliferator-activated receptor-gamma coactivator-1 (PPARGC1) acts as a cofactor for several nuclear hormone receptors in many tissues and organs implicated in blood pressure regulation. Here, we assessed the association between the Gly482Ser variant of PPARGC1 and the arterial hypertension frequently found in subjects with type 2 diabetes.Methods. We studied a group of 479 men and 253 women with type 2 diabetes. Arterial hypertension was present in 70% of the men and in 73% of the women. Genotypes were examined by PCR restriction fragment length polymorphism. A logistic regression analysis was performed to assess the covariables associated with arterial hypertension.Results. There was an association between Ser allele homozygosis and arterial hypertension in type 2 diabetic men (odds ratio of 2.52 vs Gly allele homozygosis; 95% CI: 1.32-5.00; p=0.0064), but not in women. the prevalence of arterial hypertension in type 2 diabetic men was 77% vs 73% vs 67% for Ser-Ser, Gly-Ser and Gly-Gly carriers respectively (p=0.021). Age, BMI, the use of insulin, and triglyceride and creatinine levels were also independently associated with arterial hypertension in this cohort.Conclusions/interpretation. We have observed a sex-specific association between the PPARGC-1 gene Gly482Ser polymorphism and arterial hypertension in type 2 diabetic men. Further studies are needed to investigate the genetic, biochemical and pathophysiological basis of this allelic association.
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    Interleukin-6 polymorphisms and the risk of cervical cancer
    (Blackwell Publishing, 2006-05-01) Souza, NCN de; Brenna, SMF; Campos, F.; Syrjanen, K. J.; Baracat, Edmund Chada [UNIFESP]; Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Leonor Mendes Barros Matern Hosp; Turku Univ
    Recent data implicate that cytokine gene polymorphisms are important in pathogenesis of various neoplastic and nonneoplastic human diseases, and it was recently suggested that polymorphisms in interleukin (IL)-6 might increase the risk of gynecological malignancies, including cervical carcinomas. The aim of this case-control study is to compare the IL-6 polymorphisms in cervical cancer patients and healthy controls and to assess whether any of these polymorphisms would increase the risk of developing cervical cancer. The material in this case-control study consists of 56 patients with cervical carcinoma and 253 population-based control subjects, all ethnic Brazilian women. Control subjects were cancer-free women, following a negative cervical cytology and colposcopy. IL-6 genotyping was performed using a polymerase chain reaction-based restriction fragment length polymorphism. Distribution of the GG, GC, and CC genotypes in cases and controls was significantly different (P = 0.033). Compared with the GG genotype as reference, the adjusted odds ratio for the combined GC and CC genotypes in cancer patients was 1.90 (95% confidence interval, 1.1-3.4). These data suggest that women carrying at least one C genotype in their IL-6 promoter region (-174G -> C) are at higher risk of developing cervical cancer.
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    Mutations in the HFE gene (C282Y, H63D, S65C) in a Brazilian population
    (Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular, 2006-12-01) Bueno, Simone [UNIFESP]; Duch, Cibele R. [UNIFESP]; Figueiredo, Maria Stella [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Hereditary hemochromatosis (HH) is the most common genetic disorder occurring in individuals of northern European descent. The clinical characteristic of this disease is the gradual accumulation of iron in internal organs, which ultimately leads to organ failure and death. The defective gene in the majority of cases, HFE, was identified in 1996. Three allelic variants of the HFE gene have been correlated with HH: C282Y is significantly associated with HH; H63D and S65C have unclear relationships. In this report, these mutations were analyzed in 8 patients with HH and in 148 healthy individuals (blood donors). To detect the mutations, exons 2 and 4 of the HFE gene were amplified by PCR followed by restriction endonucleases cleavage. In patients with HH, three individuals were homozygous for the C282Y mutation, one showed compound heterozygous (C282Y/H63D), one was heterozygous for the C282Y and 3 presented with no mutations. In healthy individuals, the allele frequency observed was 0.014 for C282Y, 0.108 for H63D and 0.010 for S65C. The frequency of mutations was significantly higher in Caucasians compared with non-Caucasians. These data are concordant with the previous literature and with the ethnical origin of the population studied.
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    Prevalence of myocardial infarction is related to hyperhomocysteinemia but not influenced by C677T methylenetetrahydrofolate reductase and A2756G methionine synthase polymorphisms in diabetic and non-diabetic subjects
    (Elsevier B.V., 2005-05-01) Helfenstein, T.; Fonseca, FAH; Relvas, WGM; Santos, A. O.; Dabela, M. L.; Matheus, SCP; D'Almeida, V; Tufik, S.; Souza, F. G.; Rodrigues, P. R.; Taglieri, R.; Sousa, E. F.; Izar, MCO; Universidade Federal de São Paulo (UNIFESP)
    Background: Hyperhomocysteinemia has emerged as a novel risk factor for myocardial infarction (MI). Some mechanisms proposed to explain its relationship with coronary events are also shared by major coronary risk factors. We examined whether C677T methylenetetrahydrofolate reductase and A2756G methionine synthase polymorphisms could affect the relative risk for MI.Methods: A sample of 196 individuals was divided into four groups (diabetics with MI, n=43; diabetics without MI, n=50; non-diabetics with MI, n=47; non-diabetics without MI, n=56) and compared regarding the prevalence of the polymorphisms, risk factors, and biochemical parameters.Results: Higher prevalence of hyperhomocysteinemia was found in MI patients (p < 0.05 vs. non-MI subjects), in males (p < 0.001 vs. female) and in those >= 65 years (p=0.01 vs. < 65 years). Homocysteine was negatively associated with HDL-C (p < 0.05) and glucose, although results did not reach significance (p=0.06). Similar distribution of studied polymorphisms was seen in all groups, which presented normal folate and vitamin B12 serum levels.Conclusions: Higher homocysteinemia was predominantly observed in men, presenting low HDL-C, and at advancing age. Methylenetetrahydrofolate reductase and methionine synthase polymorphisms did not contribute to risk assessment in diabetic and non-diabetic subjects presenting normal folate levels. (c) 2005 Elsevier B.V. All rights reserved.
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    Relationship between gene polymorphisms and prevalence of myocardial infarction among diabetic and non-diabetic subjects
    (Elsevier B.V., 2005-01-01) Relvas, WGM; Izar, MCO; Helfenstein, T.; Fonseca, MIH; Colovati, M.; Oliveira, A.; Ihara, SSM; Han, S. W.; Casas, AAL; Fonseca, FAH; Universidade Federal de São Paulo (UNIFESP)
    This study was aimed to examine cholesteryl ester transfer protein (CETP). apolipoprotein AI and CIII gene polymorphisms. and to verify whether these genetic determinants are associated with the prevalence of myocardial infarction (MI) or type 2 diabetes. the TaqIB restriction fragment length polymorphism (RFLP) in intron I of the CETP gene. the Mspl in the third intron of the APOAI gene. and also Ssrl in the 3' untranslated region of the APOCIII gene were determined using standard methods. the prevalence of these, polymorphisms was compared between diabetic (n = 119), and non-diabetic (n = 100) middle-aged individuals of both sexes. We found a higher prevalence of the B2B2 genotype of the CETP gene among diabetics than that observed in non-diabetics (P < 0.05), and a lower prevalence of this genotype among patients with previous MI (P < 0.02). the Mspl polymorphisms of the APOA1 gene showed that M1 divided by divided by genotype was found mainly in diabetic patients (P < 0.04). Conversely, the SstI polymorphism of APOCIII gene was not significantly associated with either MI or diabetes. Therefore, among these genetic polymorphisms. TaqIB of CETP and Mspl of apolipoprotein AI appeared to help significantly to identify diabetic individuals. in particular, the former may have an additional role in the primary prevention of coronary disease. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
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    Single-nucleotide polymorphisms in genes related to the hypothalamic-pituitary-adrenal axis as risk factors for posttraumatic stress disorder
    (Wiley, 2017) Carvalho, Carolina M [UNIFESP].; Coimbra, Bruno M. [UNIFESP]; Ota, Vanessa K. [UNIFESP]; Mello, Marcelo F. [UNIFESP]; Belangero, Sintia I. [UNIFESP]
    Posttraumatic stress disorder (PTSD) is a common psychiatric disorder. The etiology of PTSD is multifactorial, depending on many environmental and genetic risk factors, and the exposure to life or physical integrity-threatening events. Several studies have shown significant correlations of many neurobiological findings with PTSD. Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is strongly correlated with this disorder. One hypothesis is that HPA axis dysfunction may precede the traumatic event, suggesting that genes expressed in the HPA axis may be involved in the development of PTSD. This article reviews molecular genetic studies related to PTSD collected through a literature search performed in PubMed, MEDLINE, ScienceDirect, and Scientific Electronic Library Online (SciELO). The results of these studies suggest that several polymorphisms in the HPA axis genes, including FKBP5, NR3C1, CRHR1, and CRHR2, may be risk factors for PTSD development or may be associated with the severity of PTSD symptoms.
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    Trombose venosa cerebral - aspectos epidemiológicos e avaliação de polimorfismos dos genes das cadeias alfa e gama do fibrinogênio
    (Universidade Federal de São Paulo (UNIFESP), 2014-05-28) Vaez, Rodrigo [UNIFESP]; Morelli, Vania Maris Morelli [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Background: cerebral venous thrombosis (CVT) is an uncommon disease with a wide spectrum of clinical manifestations and their risk factors not yet fully elucidated. Objectives: we conducted a case-control study with the following objectives: (1) to describe the epidemiological characteristics of patients with CVT; (2) assess whether some of the fibrinogen gene polymorphisms are risk factors for deep vein thrombosis (DVT) of lower limbs and/or pulmonary embolism (PE), if they are in linkage disequilibrium (LD) in the study population and if these polymorphisms influence plasma fibrinogen levels in healthy controls. Patients and methods: we evaluated 88 patients with CVT, 194 patients with first event of lower limbs DVT and/or PE and 241 healthy individuals. Polymorphisms 6534A>G FGA, 10034C>T FGG, 1691G>A F5 and 20210G>A F2 were investigated. Results: among patients with CVT there was a predominance of women (82%) with a median age of 32 years, the most common symptom was headache (88%) and transverse sinuses were the most frequently affected sites (66%). The presence of the rare allele polymorphism 6534A>G FGA and 10034C>T FGG did not behave as a risk factor for CVT. In patients with spontaneous DVT of the lower limbs and/or PE or associated with oral contraceptive (OC), the presence of the rare allele polymorphism 6534A>G FGA (OR = 1,9; 95% CI 1,1 - 3,1) and 10034C>T FGG (OR = 1,7; 95% CI 1,1 - 2,8) behaved as a risk factor of venous thrombosis. Both polymorphisms are in strong LD in the studied population (D' = 0,866; LOD = 84,33 and r2 = 0,538). There was no difference in plasma levels of fibrinogen in healthy individuals between the genotypes of polymorphisms 6534A>G FGA and 10034C>T FGG. Conclusion: among patients with CVT there was a predominance of young women in the third decade of life and mostly exposed to the use of OC, headache was the most common clinical manifestation. Compared to the control group, the polymorphisms 10034C>T FGG and 6534A>G FGA were not risk factors for CVT. Compared to the control group, polymorphisms 10034C>T FGG and 6534A>G FGA were associated only with spontaneous DVT of the lower and/or PE or triggered by the use of OC. Polymorphisms 10034C>T FGG and 6534A>G FGA are in strong LD in control group and in patients with venous thrombosis. Polymorphisms 10034C>T FGG and 6534A>G FGA did not affect plasma fibrinogen levels in healthy controls.