الفهرس 
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Abstract
AD is the most widely recognized reason for dementia and a major public health problem. AD is a genetically heterogeneous disorder of CNS. It is a progressive brain disorder that cause memory loss and related with unusual behaviour, personality changes and an irreversible decline in thinking ability. The brain of an AD patient has a bounty of plaques and tangles. Plaques are stores of beta amyloid (Aβ) protein fragments that form in the spaces between nerve cells. Tangles are twisted filaments of another protein that builds up within the cells called tau protein.
There are numerous hereditary loci which adjust AD hazard. The main known risk factor for AD is APOE ε4. Other genetic loci markers for AD risk included rs3764650 polymorphism in the ABCA7 gene, rs11136000 polymorphism in the CLU gene, and rs610932 polymorphism in the MS4A6A gene, that were identified in GWAS. These polymorphisms are on the “AlzGene Top Results” list which outlines the most settled genes related to AD.
As genetics for AD in Egyptian population need to be explored, so the aim of the current study was to investigate the association of ABCA7 rs3764650, CLU rs11136000 and MS4A6A rs610932 genetic variants with AD in a sample of Egyptian patients hoping to establish molecular biomarkers for early detection of the susceptibility to develop AD and therefore early treatment of this neurodegenerative disease.
from peripheral blood, DNA was extracted. Genotyping was done in 100 Alzheimer patients 60 years old or above and 100 age and sex matched cognitively normal controls using conventional PCR followed by restriction fragment length polymorphism (RFLP). Informed consent was obtained from all participants (Approval Number: 18135). DNA sequencing was done to confirm the results of RFLP.
The data were analyzed using Microsoft Excel 2010 and SPSS version 24.0 (SPSS IBM., Chicago, IL). Continuous normally distributed variables were represented as mean ± SD. With 95% confidence interval, and using the frequencies and percentage for categorical variables, the level of significance with P ≤ 0.05 was considered statistically significant, P ≤ 0.01 was considered of high significance and P > 0.05 insignificant.
There was no significant difference between the two studied groups in the genotype distribution and allele frequency of the rs3764650 SNP in ABCA7 gene. The minor allele frequency G was (7%) in AD patients group and (8%) in the control group. The variant CC of rs11136000 SNP in CLU gene was lower in AD patients compared to controls (AOR= 2.314, 95% CI = 1.079 – 4.964, P= 0.03*) in respect to the TT genotype. There was no significant difference between the two groups with respect to the CT and TT variant genotypes. The minor allele frequency T in AD patients and controls was 18% and 13%, respectively.
No significant difference regarding the genotype distribution and allele frequency of rs610932 SNP in MS4A6A gene was demonstrated between the AD patients and controls where the minor allele frequency C was (42%) and (40%) in AD patients and controls, respectively.
The genotypic data of the three evaluated variants were stratified according to the APOE ε4 status in AD patients. APOE ε4 carriage were significantly associated with CT genotype of CLU rs11136000 gene (P = 0.003). Among AD patients, the frequency of the CLU CC genotype was lower in APOE ε4 allele carriers APOE ε4 allele non-carriers with a significant difference (P = 0.003). However, there was no significant association between APOE ε4 and ABCA7 rs3764650 or MS4A6A rs610932 genotypes (P = 0.37 and 0.9, respectively).
We concluded that AD not associated with the MS4A6A rs610932 and ABCA7 rs3764650, but CLU rs11136000 has lower association with AD. Future genetics studies on AD enrolling a larger number of Egyptian patients from different geographic locations as multi-center national studies are recommended to unmask such complex disorder.