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Capobianco M.P.,Sao Paulo State University | Cassiano G.C.,Sao Paulo State University | Storti-Melo L.M.,Federal University of Sergipe | Pavarino E.C.,Unidade de Pesquisa em Genetica e Biologia Molecular | And 4 more authors.
Transactions of the Royal Society of Tropical Medicine and Hygiene

Background: Plasmodium vivax is the most prevalent malaria species in Brazil. The parasite-host coevolutionary process can be viewed as an 'arms race', in which adaptive genetic changes in one are eventually matched by alterations in the other. Methods: Following the candidate gene approach we analyzed the CD40, CD40L and BLYS genes that participate in B-cell co-stimulation, for associations with P. vivax malaria. The study sample included 97 patients and 103 controls. We extracted DNA using the extraction and purification commercial kit and identified the following SNPs: 21C.T in the CD40 gene, 2726T.C in the CD40L gene and the 2871C.T in the BLyS gene using PCR-RFLP. We analyzed the genotype and allele frequencies by direct counting. We also compared the observed with the expected genotype frequencies using the Hardy-Weinberg equilibrium. Results: The allele and genotype frequencies for these SNPs did not differ statistically between patient and control groups. Gene-gene interactions were not observed between the CD40 and BLYS and between the CD40L and BLYS genes. Overall, the genes were in Hardy-Weinberg equilibrium. Significant differences were not observed among the frequencies of antibody responses against P. vivax sporozoite and erythrocytic antigens and the CD40 and BLYS genotypes. Conclusions: The results of this study show that, although the investigated CD40, CD40L and BLYS alleles differ functionally, this variation does not alter the functionality of the molecules in a way that would interfere in susceptibility to the disease. The variants of these genes may influence the clinical course rather than simply increase or decrease susceptibility. © Royal Society of Tropical Medicine and Hygiene 2013. All rights reserved. Source

Ruiz M.T.,Unidade de Pesquisa em Genetica e Biologia Molecular | Biselli P.M.,Unidade de Pesquisa em Genetica e Biologia Molecular | Pavarino-Bertelli E.C.,Unidade de Pesquisa em Genetica e Biologia Molecular | Goloni-Bertollo E.M.,Unidade de Pesquisa em Genetica e Biologia Molecular
Brazilian Journal of Medical and Biological Research

Vascular endothelial growth factor (VEGF) is one of the most potent endothelial cell mitogens and plays a critical role in angiogenesis. Polymorphisms in this gene have been evaluated in patients with several types of cancer. The objectives of this study were to determine if there was an association of the -1154G/A polymorphism of the VEGF gene with head and neck cancer and the interaction of this polymorphism with lifestyle and demographic factors. Additionally, the distribution of the VEGF genotype was investigated with respect to the clinicopathological features of head and neck cancer patients. The study included 100 patients with histopathological diagnosis of head and neck squamous cell carcinoma. Patients with treated tumors were excluded. A total of 176 individuals 40 years or older were included in the control group and individuals with a family history of neoplasias were excluded. Analysis was performed after extraction of genomic DNA using the real-time PCR technique. No statistically significant differences between allelic and genotype frequencies of -1154G/A VEGF polymorphism were identified between healthy individuals and patients. The real-time PCR analyses showed a G allele frequency of 0.72 and 0.74 for patients and the control group, respectively. The A allele showed a frequency of 0.28 for head and neck cancer patients and 0.26 for the control group. However, analysis of the clinicopathological features showed a decreased frequency of the A allele polymorphism in patients with advanced (T3 and T4) tumors (OR = 0.36; 95%CI = 0.14-0.93; P = 0.0345). The -1154A allele of the VEGF gene may decrease the risk of tumor growth and be a possible biomarker for head and neck cancer. This polymorphism is associated with increased VEGF production and may have a prognostic importance. Source

Mendes C.C.,Unidade de Pesquisa em Genetica e Biologia Molecular | Raimundo A.M.Z.D.A.,Unidade de Pesquisa em Genetica e Biologia Molecular | Oliveira L.D.,Unidade de Pesquisa em Genetica e Biologia Molecular | Zampieri B.L.,Unidade de Pesquisa em Genetica e Biologia Molecular | And 9 more authors.
Genetic Testing and Molecular Biomarkers

Background: Down syndrome (DS) results from the presence and expression of three copies of the genes located on chromosome 21. Studies have shown that, in addition to overexpression of the Cystathionine β-synthase (CBS) gene, polymorphisms in genes involved in folate/homocysteine (Hcy) metabolism may also influence the concentrations of metabolites of this pathway. Aim: Investigate the association between Dihydrofolate reductase (DHFR) 19-base pair (bp) deletion and Serine hydroxymethyltransferase (SHMT) C1420T polymorphisms and serum folate and plasma Hcy and methylmalonic acid (MMA) concentrations in 85 individuals with DS. Methods: Molecular analysis of the DHFR 19-bp deletion and SHMT C1420T polymorphisms was performed by polymerase chain reaction (PCR) by difference in the size of fragments and real-time PCR allelic discrimination, respectively. Serum folate was quantified by chemiluminescence and plasma Hcy and MMA by liquid chromatography-tandem mass spectrometry. Results: Individuals with DHFR DD/SHMT TT genotypes presented increased folate concentrations (p=0.004) and the DHFR II/SHMT TT genotypes were associated with increased MMA concentrations (p=0.008). In addition, the MMA concentrations were negatively associated with age (p=0.04). Conclusion: There is an association between DHFR DD/SHMT TT and DHFR II/SHMT TT combined genotypes and folate and MMA concentrations in individuals with DS. © Copyright 2013, Mary Ann Liebert, Inc. 2013. Source

Zampieri B.L.,Unidade de Pesquisa em Genetica e Biologia Molecular | Biselli-Perico J.M.,Unidade de Pesquisa em Genetica e Biologia Molecular | De Souza J.E.S.,University of Sao Paulo | De Souza J.E.S.,Institute of Bioinformatics and Biotechnology 2Bio | And 8 more authors.

Individuals with Down syndrome (DS) have a high incidence of immunological alterations with increased susceptibility to bacterial and viral infections and high frequency of different types of hematologic malignancies and autoimmune disorders. In the current study, we profiled the expression pattern of 92 immune-related genes in peripheral blood mononuclear cells (PBMCs) of two different groups, children with DS and control children, to identify differentially expressed genes that might be of pathogenetic importance for the development and phenotype of the immunological alterations observed in individuals with DS. PBMCs samples were obtained from six DS individuals with karyotypically confirmed full trisomy 21 and six healthy control individuals (ages 2-6 years). Gene expression was profiled in duplicate according to the manufacturer's instructions provided by commercially available TaqMan Human Immune Array representing 92 immune function genes and four reference genes on a 96-plex gene card. A set of 17 differentially expressed genes, not located on chromosome 21 (HSA21), involved in immune and inflammatory pathways was identified including 13 genes (BCL2, CCL3, CCR7, CD19, CD28, CD40, CD40LG, CD80, EDN1, IKBKB, IL6, NOS2 and SKI) significantly down-regulated and four genes (BCL2L1, CCR2, CCR5 and IL10) significantly up-regulated in children with DS. These findings highlight a list of candidate genes for further investigation into the molecular mechanism underlying DS pathology and reinforce the secondary effects of the presence of a third copy of HSA21. © 2014 Zampieri et al. Source

Proenca M.A.,Sao Paulo State University | Fernandes G.M.M.,Unidade de Pesquisa em Genetica e Biologia Molecular | Russo A.,Unidade de Pesquisa em Genetica e Biologia Molecular | Lelis R.B.,Unidade de Pesquisa em Genetica e Biologia Molecular | And 3 more authors.
Genetics and Molecular Research

Polymorphisms in genes encoding P450 cytochrome enzymes may increase the risk of sporadic colorectal cancer (SCRC). Here we investigated the association between SCRC and CYP2E1 (PstI) and CYP1A1 (MspI) polymorphisms in a case-control study. Moreover, we sought to determine any possible associations between this disease and the sociodemographic factors. We included 273 individuals (74 patients and 199 controls); the gender, age, tobacco usage, and alcohol consumption of the included subjects, and the clinico-histopathological parameters of the tumors, were analyzed. Molecular analyses were performed using PCR-RFLP. The effect of polymorphisms on SCRC development, and the association between this disease and sociodemographic factors were determined by multiple-logistic regression analyses. The combined genotype was also evaluated. Statistically significant differences between the patients and controls regarding the male gender (odds ratio, OR = 0.19, 95% confidence interval, CI = 0.08-0.46; P ≤ 0.05) and age ≥44 years (median = 44; OR = 96.84, 95%CI = 21.78-430.49; P ≤ 0.05) were observed. The evaluated polymorphisms were not associated with SCRC (PstI-CYP2E1: OR = 0.93, 95%CI = 0.30-2.85; P = 0.897; MspI-CYP1A1: OR = 0.75, 95%CI = 0.35-1.61; P = 0.463); the combined genotypes were not associated with the risk of disease. Thus, individuals aged ≥44 years are more sensitive to SCRC, while men are less susceptible. Additionally, polymorphisms in CYP2E1 (PstI) and CYP1A1 (MspI) were not associated with SCRC in the evaluated Brazilian population. © FUNPEC-RP. Source

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