| 1. ObjectiveDementia is a cognitive handicap with a high morbidity in old people. The clinical features are developed memory deficits and progressive loss of cognitive abilities. Part of them are accompanied by psychiatric symptoms and abnormal feelings. In China, dementia includes sporadic Alzheimer's disease and vascular dementia mainly. It's reported that ApoE e 4 allele, missense or polymorphism of ps-1 gene and mutation of MTHFR gene are associated with SAD. Research found that ApoE gene polymorphism and MTHFR gene mutation are related to vascular dementia. Among them, ApoE e 4 allele associated with SAD has been confirmed, the others are not final conclusion. In China no report on relationship between E318G missense mutation of PS-1 and dementia is found at present, no material that discuss the association of MTHFR gene mutation and VD is found, too. In addition, the reported ApoE e 4 allele frequency is variant in different area in China. In order to detect the ApoE E 4 allele frequency of dementia patients and discuss the relationship of these genes polymorphisms or mutations and dementia in Beijing China, we detected the polymorphism of ApoE gene, polymorphism of 3'intron to 8 exon of ps-1 gene, ps-1 gene E318G missense mutation, MTHFR gene C677T mutation in different groups and address the relationship between these genetic factors and dementia as well as the cooperation of these genetic factors for dementia. If possible, we will offer molecular biology markers for clinic diagnosis of dementia.2. methodsPeripheral blood samples of dementia patients were collected from hospitals or bureau of military retiree of Beijing city, including 135 cases of SAD and 29 cases VD. Blood samples of control came from social peoples in Wanshou Road area of Beijing city, All of them are healthy aged people(^65 years old), MMSE scored28, totally 138 cases, diagnosis of SAD and VD act as the criterion of ICD-10, all of the patients have supporting image reference and followed more one year. DNA was prepared by standard proteinase K digestion and phenol/chloroform extraction method from blood samples. The PCR-RFLP method was used to analyse the genotypes or mutations of ApoE, ps-1 and MTHFR gene. Allele frequencies and mutation frequencies were calculated. Stata4.0 medical statistical software was used for data statistic analysis. 3. ResultsApoE polymorphism and dementia ApoE ?2 allele frequencies of NC, SAD and VD group were 6.16%, 4.81% and 10.34%, respectively. ApoE t 3 allele frequencies of NC, SAD and VD group were 88.04%, 84.44% and 86.21%, respectively. ApoE 4 allele frequencies of NC, SAD and VD group were 5.80%, 10.74% and 0.35%, respectively. The distribution of ApoE e 4 allele frequencies between SAD and NC group was significant difference by statistical analysis (p<0.05), OR values were 1.95.Ps-1 polymorphism and dementia 1 allele frequencies of 3'intron to 8 exon of ps-1 in NC, SAD and VD group were 69.20%, 61.10% and 56.90%, respectively. 2 allele frequencies of the polymorphic site in NC, SAD and VD group were 30.80%, 38.90% and 43.10%, respectively. The distribution of 2 allele frequencies was significant different by statistical analysis between SAD and NC group (p<0.05), OR values were 1.43. The distribution of 1/2 and 2/2 genotypes was significant differentbetween VD and NC group statistically (p<0.05), OR values were 0.53 and 5.76, respectively.Ps-1 missense mutation and dementia ps-1 E318G missense mutation was not detected in three groups.MTHFR mutation and dementia The frequencies of MTHFR C677T mutation in NC, SAD and VD group were 43.8%, 46.3% and 51.7%, respectively. No significant difference was found between the different groups statistically.Synergistic action of ApoE and ps-1 polymorphism In parts of samples with 2 allele of 3'intron to 8 exon polymorphism of ps-1, the ApoE ?4 allele frequency distribution was significant different between SAD and NC group, but no difference was found between VD and NC group.Synergistic action of ApoE and MTHFR mu...
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