RESUMO
OBJECTIVES: The risk of sporadic cerebral amyloid angiopathy (CAA) may be associated with genetic polymorphisms of molecules related to anabolism or catabolism of amyloid beta protein (Abeta). The authors investigated whether a polymorphism of the gene (NEP) coding for neprilysin, an enzyme catabolising Abeta, is associated with CAA. METHODS: The study analysed the GT repeat polymorphism in the enhancer/promoter region of NEP and severity of CAA in 164 necropsied elderly Japanese subjects. RESULTS: The subjects had NEP polymorphisms with 19 to 23 GT repeats and were classified into nine genotypes. CAA severity was significantly higher in the subjects with up to 40 repeats in total than those with more than 40 repeats (p=0.005). There was a significant correlation between the number of the shorter alleles (19 or 20 repeats) and CAA severity (p=0.024). In addition, there was no interaction between the NEP polymorphism and apolipoprotein E genotype. CONCLUSIONS: These results suggest the association between the NEP polymorphism and the risk of CAA. Further study using more samples from populations with different ethnic backgrounds is necessary.
Assuntos
Angiopatia Amiloide Cerebral/enzimologia , Angiopatia Amiloide Cerebral/genética , Neprilisina/metabolismo , Polimorfismo Genético/genética , Receptores Proteína Tirosina Quinases/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Apolipoproteínas E/genética , Angiopatia Amiloide Cerebral/patologia , Técnicas de Cultura , Receptor com Domínio Discoidina 1 , Feminino , Genótipo , Humanos , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genéticaAssuntos
Doença de Alzheimer/enzimologia , Doença de Alzheimer/genética , Neprilisina/genética , Polimorfismo Genético/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Autopsia , Estudos de Casos e Controles , Repetições de Dinucleotídeos/genética , Repetições de Dinucleotídeos/fisiologia , Frequência do Gene , Marcadores Genéticos/genética , Genótipo , Humanos , Pessoa de Meia-Idade , Neprilisina/fisiologia , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Previous study has shown that the anti-Hu antibody titre of serum samples from patients with paraneoplastic encephalomyelitis/paraneoplastic sensory neuronopathy (PEM/PSN) was significantly higher than that from patients with small cell lung cancer without neurological disturbances (non-PEM/PSN). The aims of this study were (1) to identify the fine epitopes on HuD recognised by the anti-Hu antibody, (2) to determine if the pattern of epitopic reactivity differed between antibodies from patients with and without PEM/PSN, and (3) to determine if the pattern of epitopic reactivity correlated with the clinical features. Recombinant full length HuD and nine deletion fragments were constructed and immunoreacted by western blot analysis with 14 anti-Hu serum samples from eight patients with PEM/PSN and six without PEM/IPSN. All anti-Hu serum samples reacted with the deletion fragments containing amino acids (aa) 90-101 or aa 171-206. Some anti-Hu samples reacted with the deletion fragments containing aa 223-234, aa 235-252, or aa 354-373. There was no difference in the pattern of epitopic reactivity between patients with and without PEM/PSN. There was no correlation between the pattern of epitopic reactivity and the clinical features. The anti-Hu antibody titre from patients with PEM/ PSN was significantly higher than from patients without PEM/PSN, but there was overlap of their titre concentrations. In conclusion, aa 90-101 and aa 171-206 are the major epitopes with which all anti-Hu serum samples react, and aa 223-234, aa 235-252, and aa 354-373 are the minor epitopes with which only some anti-Hu serum samples react. The analyses suggested that the pattern of epitopic reactivity of the anti-Hu antibody on HuD was not a critical factor for the development or clinical features of PEM/PSN.