RESUMO
We analyzed association of potentially regulatory polymorphisms (rs590352, rs11542583, rs3829202, rs207258, and rs4796672) with breast cancer. A significant association was found between this disease and rs2072580T>A (p=0.001) located in the overlapping promoter regions of the SART3 and ISCU genes. In women with AA and AT genotypes, the risk of breast cancer is higher by 6.7 times (p=0.001) and 12 times (p=0.001), respectively, in comparison with TT genotype. Under a codominant model of inheritance (AT vs AA+TT), the risk of breast cancer was increased by 4.2 times (Ñ=0.001) for the AT genotype. Under a recessive model of inheritance (TT vs AA+TT), the risk of disease was 10-fold higher (Ñ=0.001) for the TT genotype. It has been demonstrated that the T>A substitution affects the binding properties of transcription factors CREB1 and REST.
Assuntos
Antígenos de Neoplasias/genética , Neoplasias da Mama/genética , Proteínas Ferro-Enxofre/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Proteínas de Ligação a RNA/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Federação Russa/epidemiologia , Adulto JovemRESUMO
Proteoglycans (PG) are involved in the brain development as well as in the pathogenesis of age-related neurodegenerative disorders but underlying mechanism remains poorly understood. We showed that senescence-accelerated OXYS rats are suitable model of age-related cerebral dysfunctions. Here the content and composition of PG in the postnatal development and during behavioral decline were examined in the brain of OXYS and Wistar(control) rats at the ages of 1, 7, 14 days and 1, 2 and 14 months. Thereafter behavior in open field (OF) and elevated plus maze (EPM) was investigated. Data confirmed the absence of differences in the performance in tasks between Wistar and OXYS rats at the age of 1 month and showed faster age-related anxiety-like behavior decline in OXYS rats. The distribution of PG and the extent of their sulfation undergo dramatic and rapid changes in the brain during postnatal development both in Wistar and OXYS rats. Significant differences in these parameters appeared in the period of development of behavioral decline in OXYS rats. In contrast, no interstrain differences were revealed in the content and composition of PG in 14-month-old rats when behavior deteriorations are already developed. The results suggest that behavioral deterioration in OXYS rats occurs against the background of altered composition, quantity and glycosaminoglycans (GAG) sulfation.
