Análisis de polimorfismos de genes relacionados con la función endotelial y la muerte celular en demencia vascular y enfermedad de alzheimer

[EN] INTRODUCTION : Alzheimer 's disease ( AD) and vascular dementia (VD ) , the two most common causes of dementia, represent a major health problem . The onset of dementia may be determined by genetic and environmental factors. EA and DV share pathogenic mechanisms such as endothelial dysfunction and cell death . Single nucleotide polymorphisms ( SNPs ) of genes encoding vascular endothelial growth factor ( VEGF-A ) and its receptor ( VEGFR-2) , endothelial nitric oxide synthase (eNOS ) or the tumor suppressor protein ( Tp53 ) might regulate the risk of these dementias. OBJECTIVES : Analyze the relationship of SNPs - 460C > T and - 2578A > C of VEGFA gene, - 604A > G of the VEGFR2 gene +894 G > T of the eNOS gene and the Tp53 Arg72Pro gene as well as sociodemographic and clinical risk factors DV develop ( and its subtypes ) and EA . PATIENTS AND CONTROLS: We conducted a case-control study which included 150 patients with DV ( DV 74 cortical and subcortical DV 76 ) , 147 patients with AD and 150 controls over 70 years that there was no evidence of clinical or psychometric cognitive impairment. Clinical data and blood samples were collected . Genotyping was accomplished by DNA digestion with restriction nucleases (PCR -RFLP ) and PCR with Taqman probes ( qRT- PCR ) . RESULTS : The population included in our study , allele - 460C - 2578A and the VEGFA gene (OR : 0.625 , P = 0.042 ) and +894 G allele of the eNOS gene ( OR: 0.606 , P = 0.037 ) were associated with lower risk of EA in over 80 years. The - 604A allele of the VEGFR2 gene ( OR: 0.555 , P = 0.004 ) was associated with a lower risk of subcortical DV . The Pro72 allele of Tp53 gene (OR : 0.500 , P = 0.001 ) was associated with a lower risk of AD and the Arg72 allele (OR : 1.768 , P = 0.026 ) was associated with an increased risk of cortical DV . A low level of education has a significant influence on the development of dementia in general , and vascular risk factors in the development of DV in particular. CONCLUSIONS : The results of our study suggest that polymorphisms associated with endothelial function and cell death may vary, at least in part , the susceptibility to the risk of dementia.

Author

• Manso Calderón, Raquel

• Academic dissertations
• clinical genetics
• Neurology
• Tesis y disertaciones académicas
• Universidad de Salamanca (España)
• Genetica clinica
• Neurología

Identifier

hdl:10366/123009

OAI identifier oai:identifier

oai:gredos.usal.es:10366/123009