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P1‐079: Impact of multiple genetic factors on the progression of Alzheimer dementia
Author(s) -
Fung Hon-Chung P.
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.627
Subject(s) - logistic regression , single nucleotide polymorphism , disease , dementia , covariate , multivariate statistics , genetic model , genotype , genotyping , genetic association , genetic architecture , candidate gene , neuropsychology , haplotype , alzheimer's disease , genetic variation , biology , cognition , genetics , medicine , gene , quantitative trait locus , psychiatry , statistics , mathematics
Background: Alzheimer’s disease (AD), at least to a significant extent, is known to be caused by inheritance trait. There are numerous genetic polymorphisms have been linked to the prevalence of AD. Most of those genetic studies concern only about solitary gene. And even fewer researches, if any, have been conducted for dissecting the genetic impact on the progression of the disease. We hypothesized that AD, as a complex genetic disorder, should be under the influence of multiple genes simultaneously. In this presentation, the impact of multiple genetic factors and its magnitude on the progression of AD will be presented. Methods: In total, 300 participants (250 AD patients and 50 cognitive healthy individuals) have been recruited and followed up for 2 years. The demographical data of each participant has been recorded as the covariates in the final analysis. And each participant has been followed up with comprehensive neuropsychological assessments (including CASI, MMSE and CDR) for baseline and follow-up evaluation. The change in their cognitive function over time will be calculated and used as the dependent variables in our multivariate logistic regression model analysis. The allelele, genotype and haplotype frequencies of the study genes (ApoE, MAPT, PS1, PS2 and APP) of each participant will be determined by genotyping the tagged SNPs over the genetic span of those genes. ANOVA and chi-square test has been used for testing the association between the genetic variants and the progression of the disease. Meanwhile, multivariate logistic regression model will be performed for analyzing the strength of association between those genetic factors and the disease progression after adjustment of the covariates. Results: Our preliminary results have shown an association between the haplotype of MAPT and the rate of progression of Alzheimer disease; meanwhile there are several covariates noted to exert some impact of the progression. Conclusions: The impact of multiple genetic factors and its magnitude on the progression of AD has been drawn. These results will not only provide the information of basic research about the influence of gene-gene and gene-environment interaction on the AD progression, but also set up a foundation for future research on the genetic study in AD population.