Polymorphisms and haplotypes of the interleukin 2 gene are associated with an increased risk of gastric cancer. The possible involvement of Helicobacter pylori.

Interleukin 2 (IL-2) is a pro-inflammatory cytokine that is mainly synthesized by immunoregulatory T helper cells and which plays an important role in antitumor immunity. Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the gastric mucosa and induces the production of IL-2. This process increases the magnitude of inflammation and may influence the development of gastric pathologies. In light of the possible involvement of IL-2 and the presence of H. pylori in gastric diseases, this study investigated possible associations between the IL-2 polymorphisms +114 T>G (rs2069763) and -330 T>G (rs2069762) and the development of gastric cancer; these associations were then correlated with the presence of H. pylori. Gastric biopsies were obtained from 294 dyspeptic patients (173♀/123♂). Of these samples, 181 were chronic gastritis samples (102♀/79), 62 were samples of intact gastric mucosa (47♀/15♂), and 51 were samples of gastric cancer (22♀/29♂). PCR-RFLP was used to characterize the +114 T>G and -330 T>G polymorphisms. Considering the genetic characteristics of the study population and based on the codominant model, a high risk of gastric cancer among patients with normal gastric tissue and patients with gastric cancer was found in subjects with the IL-2-330 GG genotype (OR=6.43, 95% CI: 1.47-28.10, p=0.044). The data was adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found among subjects with the IL-2-330 GG genotype (OR=4.47, 95% CI: 1.84-10.84, p=0.0022). When the IL-2 +114 polymorphism was analyzed, similar results were found. Among the patients with normal gastric tissue and the patients with gastric cancer, subjects carrying the +114 TT genotype were found to be at a high risk of gastric cancer (OR=5.97, 95% CI: 1.60-22.27, p=0.013). This data was also adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found in subjects carrying the +114 TT genotype (OR=6.36, 95% CI: 2.66-15.21, p<0.0001). The haplotype was also analyzed. The -330G/+114T haplotype was found to be significantly associated with gastric cancer. Therefore, our results show that, among patients with H. pylori infection, the -330 GG and +114 TT genotypes are significantly associated with a high risk of developing gastric cancer, as is the -330G/+114T haplotype.

Gene polymorphism of interleukin 1 and 8 in chronic gastritis patients infected with Helicobacter pylori

Epidemiological investigations have indicated that Helicobacter pylori induces inflammation in the gastric mucosa regulated by several interleukins. The genes IL1B and IL8 are suggested as key factors in determining the risk of gastritis. The aim of this paper was to evaluate the association of gene polymorphism of interleukin-1 and interleukin-8 with chronic gastrits in H. pylori infected patients. A total of 60 patients underwent endoscopic procedure. Biopsy samples were collected for urease test, histopathological and molecular exams. The DNA of theses samples was extracted for detection of H. pylori and analysis of the genes mentioned above. Patients with gastritis had a higher frequency of H. pylori-positive samples.

Gene polymorphism of interleukin 1 and 8 in chronic gastritis patients infected with Helicobacter pylori

Epidemiological investigations have indicated that Helicobacter pylori induces inflammation in the gastric mucosa regulated by several interleukins. The genes IL1B and IL8 are suggested as key factors in determining the risk of gastritis. The aim of this paper was to evaluate the association of gene polymorphism of interleukin-1 and interleukin-8 with chronic gastrits in H. pylori infected patients. A total of 60 patients underwent endoscopic procedure. Biopsy samples were collected for urease test, histopathological and molecular exams. The DNA of theses samples was extracted for detection of H. pylori and analysis of the genes mentioned above. Patients with gastritis had a higher frequency of H. pylori-positive samples.

Controle genético das células-tronco humanas cultivadas / Genetic control of cultivated human stem cells

As células-tronco apresentam uma alta capacidade de autorregeneração, assim como, um potencial de diferenciação em uma variedade de tipos celulares. Estas células podem ser classificadas como embrionárias e adultas. Apesar de apresentar propriedades de células-tronco, as mesenquimais apresentam um certo grau de dificuldade no estabelecimento das culturas, podendo induzir a perda da expressão da enzima responsável pela imortalização ou enzima telomerase. A enzima telomerase é considerada um relógio biológico, um indicador que a senescência celular irá se instalar inevitavelmente. A questão mais atual e intrigante dos pesquisadores é se o suposto potencial de divisão, por um determinado período de tempo, das células-tronco cultivadas poderia levar ao acúmulo de alterações genéticas e epigenéticas, resultando em um processo neoplásico. Daí a importância do papel da citogenética humana no controle e monitoramento das células-tronco cultivadas que serão utilizadas na terapia em seres humanos. Alterações cromossômicas estruturais, tais como deleções, translocações e inversões, representam um mecanismo importante pelo qual as células cancerígenas desenvolvem-se gradualmente, uma vez que estas alterações cromossômicas podem levar a uma expressão anormal de muitos genes, podendo desencadear assim o processo neoplásico.

Stem cells have a high capacity of self-regeneration, as well as a potential to differentiate into several cell types. These cells can be classified as embryonic or adult. In spite of having inherent properties of stem cells, mesenchymal cells show a certain degree of difficulty to establish cultures. This might induce a loss of the expression of the telomerase enzyme which is considered to be a biological clock or an indicator of the senescence of the cells. The most current and intriguing question for researchers is whether the presumed division potential of cultivated stem cells, over a period of time could result in an accumulation of genetic alterations and consequently, in a neoplastic process. For this reason, cytogenetic techniques are very important to guarantee the control and safety of cultivated stem cells to be used in human therapy. Structural chromosomal alterations, such as for example, deletions, translocations and inversions represent an important mechanism by which cells might gradually transform in a neoplastic process. Thus, these chromosomal alterations could result in an abnormal expression of the genes and lead to cancer.

APO A-V-1131T-->C polymorphism frequency and its association with morbidity in a Brazilian elderly population.

Identification of genetic polymorphisms as risk factors for complex diseases affecting older people can be relevant for their prevention, diagnosis and management. The -1131T-->C polymorphism of the apolipoprotein A-V gene (APO A-V) is tightly linked to lipid metabolism and has been associated with increased triglyceride levels and familial dyslipidemia. The aims of this study were to analyze the allele and genotype frequencies of this polymorphism in a Brazilian elderly population and to investigate any association between the polymorphism and major morbidities affecting elderly people. This polymorphism was investigated in 371 individuals, aged 66-97 years, in a Brazilian Elderly Longitudinal Population Study. Major morbidities investigated were: cerebrovascular diseases (CVD); myocardial infarction (MI); type 2 diabetes; hypertension; obesity; dementia; depression; and neoplasia. DNA was isolated and amplified by PCR and its products were digested with restriction enzyme Tru1I. T and C allele frequencies were 0.842 and 0.158, respectively. Our population showed allele frequencies that were similar to European and Afro-American and different from Asiatic populations. Genotype distributions were not within Hardy-Weinberg equilibrium only for the obesity subject sample. On the other hand, a significant association between the C allele and obesity in the presence of CVDxdepression interaction was observed. Logistic analysis showed no association of the polymorphism with each morbidity group. Therefore, the C allele in elderly Brazilian subjects may represent a risk factor for these morbidity interactions, which may lead to better comprehension of their pathophysiology.

Estudo clínico comparativo de prevalência sorológica de Helicobacter pylori em pacientes com urticária crônica da região de Marília, SP (Brasil) / Comparative clinical study of Helicobacter pylori seroprevalence in patients with chronic urticaria from Marília – São Paulo (Brazil)

Objetivo: Investigar se a presença de infecção porHelicobacter pylori está associada à ocorrência deurticária crônica idiopática utilizando como controledoadores de sangue do Hemocentro da Faculdade de Medicina de Marília (FAMEMA). Material e métodos: Com o emprego dos kits Enzygnostâ Anti-H. pylori II/ IgA e IgG (Dade Behring Marburg GmbH), foram comparadas as análises sorológicas anti-H. pylori de dois grupos. O primeiro com 21 pacientes com quadro clínico de urticária crônica idiopática e outro de 254 doadores de sangue. Foram ainda obtidos alguns dados epidemiológicos dos indivíduos doadores de sangue como a renda mensal familiar, o grau de escolaridade e número de pessoas na família para associação com o diagnóstico sorológico deH. pylori. As associações entre as diferentes variáveisforam analisadas estatisticamente com o emprego do teste de Qui-quadrado. Resultados: A prevalência de infecção por H. pylori determinada pelo título sorológico de IgG e/ou IgA anti H. pylori foi de 57 per cent para os dois grupos de indivíduos analisados neste estudo. Dentre os parâmetros epidemiológicos investigados, apenas o grau de escolaridade apresentou associação estatisticamente significante com o diagnóstico sorológico de H. pylori,sendo que indivíduos com até o primeiro grau tiverammaior prevalência de anticorpos IgG e/ou IgA que os indivíduos com nível superior e segundo grau (p<0,001).Conclusões: Não encontramos evidências da associação entre o H. pylori e urticária crônica, já que a prevalência de sorologia positiva na população em geralfoi a mesma encontrada para pacientes com urticária.Os dados epidemiológicos mostraram que em média, os indivíduos doadores de sangue da região de Marília possuem condições sócio-econômicas acima da média nacional brasileira e a prevalência de H. pylori nestes indivíduos é comparável aos valores encontrados para países em desenvolvimento.