| BackgroundAlzheimer’s disease (AD) is a nervous system disease, which mainly affacts the older adults. Previous studies found a number of genes might contribute to the development of AD, and apolipoprotein E (ApoE) gene has the strongest association with AD. Currently there are a large number of case and control research on the association between AD and ApoE gene and get contradictory results, so we need to system analyze the relationship between ApoE gene polymorphism and AD. On another hand, most studies have been done in different races or populations, but not in Chinese Han population. Therefore the need of a systematic analysis of the relationship between ApoE gene and AD in Chinese Han population, and compare with the results in other populations is urgent. It can provide evidence for prevention, detection and treatment of AD in Chinese Han population.There are many genotyping methods for ApoE gnee currently, and each has its advantage and disadvantage. Therefore, it is essential to clarify the the risk of Alzheimer’s disease according to the genotype of ApoE gene, and to establish a rapid method for early prevention, diagnosis and treatment of the AD.Objective1. Meta-analysis to study the relationship between ApoE gene polymorphism and Alzheimer’s disease risk in Chinese Han population. Explore the allele frequency of ApoE gene in Chinese Han population and compare with that in other populations.2. Establish and evaluate an accurate and flexible method for ApoE genotyping.Methods1. Case-control studies from 1990 to 2013 on the association of ApoE polymorphisms with Alzheimer’s disease were searched. Meta-analysis was carried out after screening through the inclusion and exclusion criteria, and the results were evaluated by sensitivity analysis and publication bias evaluation.2. Based on TaqMan-TAMRA technology, specific probes were designed, and the reaction system was optimized.1049 samples were genotyped using Taqman method andSanger sequencing were performed to confirm the genotyping results.Results1. A total of 17 studies were include and the results of Meta-analysis showed that, combined OR value and 95% confidence interval of allele ε3 was 0.38 (0.33,0.44), and that of ε4 was 4.16 (3.50,4.94). Combined OR values with 95% confidence intervals of the genotypes ε2/s3, ε3/ε3, ε3/ε4, ε4/ε4 were 0.66 (0.50,0.86),0.35 (0.30, 0.42),3.12 (2.54,3.83) and 11.34 (5.98,21.48) respectively, ε3/ε4, ε4/ε4 were risk factor in all populations, while ε2/ε4 was associated with AD only in Chinese Han polulation. E3 alleleas appeared to be protective allele in all populations, but of the protective effect was higher in Asian population than that of Caucasians and African-American populations; while ε4 allele showed risk effect in all populations, and the risk effect in Asia polulation was higher than that of in other populations. Risk allele frequency and risk effect were lower in African-American population than that of other populations, and this might partially explain the reason why AD proportion of African-American population is lower than that of other groups.2. Method for ApoE genotyping was established, which was based on the TapMan-TAMRA technology, and the reaction system was optimized. Confirmed by Sanger sequencing method, the accuracy of TaqMan-TAMRA method for ApoE genotyping was 100%.ConclusionIn conclusion, ε3 was a protective allele ands4 was a risk allele of Alzheimer’s disease in Chinese Han population. The protective genotypes for Chinese Han population are ε2/ε3 and s3/s3, while the risk genotypes are ε3/ε4 and ε4/ε4.The method for ApoE genotyping based on TaqMan-TAMRA probe technology had characteristics of high accuracy, simple operation and easy reading, and it would meet the requirement of clinical application. |
PDF Full Text Request