RESUMO
Toll-like receptor 4 is a part of the innate immune system and recognizes Helicobacter pylori lipopolysaccharide. The goal of this study was to analyze the role of Toll-like receptor 4 polymorphisms +896 (rs4986790) and +1196 (rs4986791) in the pathogenesis of Helicobacter pylori related gastroduodenal diseases in relation to gastric secretion and inflammation. Toll-like receptor 4 polymorphisms, serum gastrin-17 and pepsinogen I and II concentrations were determined, and gastroscopies with histopathological analyses were performed to 216 dyspeptic patients. As genotype controls, 179 controls and 61 gastric cancer patients were studied. In our study, the Toll-like receptor 4 +896 and +1196 polymorphisms were in total linkage disequilibrium. The homozygous wild types displayed higher gastrin-17 serum concentrations than the mutants (p = 0.001) and this effect was independent of Helicobacter pylori. The homozygous wild types also displayed an increased risk for peptic ulcers (OR: 4.390). Toll-like receptor 4 genotypes did not show any association with Helicobacter pylori positivity or the features of gastric inflammation. Toll-like receptor 4 expression was seen in gastrin and somatostatin expressing cells of antral mucosa by immunohistochemistry. Our results suggest a role for Toll-like receptor 4 in gastric acid regulation and that the Toll-like receptor 4 +896 and +1196 wild type homozygozity increases peptic ulcer risk via gastrin secretion.
Assuntos
Gastrinas/sangue , Úlcera Péptica/genética , Polimorfismo de Nucleotídeo Único , Receptor 4 Toll-Like/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrite/sangue , Gastrite/genética , Gastrite/microbiologia , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Infecções por Helicobacter/sangue , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Úlcera Péptica/sangue , Úlcera Péptica/microbiologia , Fatores de Risco , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Receptor 4 Toll-Like/metabolismo , Adulto JovemRESUMO
The aim of this study was to assess the significance of the interleukin 6 gene polymorphism -174 in gastric cancer risk. The interleukin 6 -174 G/C (rs1800795) gene polymorphisms was analyzed in gastric cancer, peptic ulcer, and nonulcer dyspepsia patients and in healthy control subjects and the data were correlated with the histopathological features of the patients' biopsies. The interleukin 6 -174 GG and GC genotypes have been previously associated with high interleukin 6 serum levels. We discovered that the interleukin 6 -174 GG and GC genotypes are associated with an increased risk of the diffuse histologic subtype of gastric carcinomas (OR: 6.809, P = 0.034), but absent in the intestinal type carcinomas (OR: 1.109, P = 0.908). No significant associations with peptic ulcer, gastric atrophy, or intestinal metaplasia were seen. Our results demonstrate that the interleukin 6 -174 GG and GC genotypes increase the risk of the diffuse type gastric carcinoma, but not the intestinal type gastric carcinoma or its precursor conditions, including atrophy or intestinal metaplasia. Thus, interleukin 6 seems to be an important carcinogenetic factor in the diffuse type gastric adenocarcinoma and its carcinogenetic effect could be noninflammatory.
Assuntos
Interleucina-6/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adulto , Idoso , Distribuição de Qui-Quadrado , Feminino , Gastrite/genética , Gastrite/patologia , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Estudos RetrospectivosRESUMO
AIM: The aim of this study was to compare the differences in health state, functional capacity and the use of social and health services among the 80-84-year-old Finnish Second World War veterans in 1992 and 2004 and to describe the possible effects of the improvements made based on the results after 1992. METHODS: The Veteran Projects were conducted among the veterans using a postal questionnaire. In 1992, the questionnaire was sent to all veterans (n = 242,720) living in Finland, and in 2004 to 5750 veterans who had participated in the study in 1992. The comparable age groups of veterans aged 80-84 years were used. The data were analysed by descriptive statistics and binary logistic regression analysis. Analyses were conducted separately for men with and without disability and for all women. RESULTS: The proportion of men with good self-reported health, painlessness, normal memory and vision and who were able to walk 500 m without difficulties, significantly increased, as did the proportion of women with normal memory and vision. The prevalence of many diseases increased, but diseases appeared to be less disabling in 2004 than 1992. The need for hospital care decreased and the use of rehabilitation services increased, but the increased use of rehabilitation services was not indicative of the ability to walk 500 m. CONCLUSIONS: Self-rated health and functional capacity improved and the need for hospital care decreased among veterans, although the prevalence of many diseases increased during the follow-up. Rehabilitation was not associated with the ability to walk 500 m without difficulties.