IDENTIFICATION AND FREQUENCY ESTIMATION OF THE 44-BP DELETION MUTATION (rs142076058) IN ABCA7 GENE AMONG ALZHEIMER PATIENTS
Project no. 447 · Status: Kapanmış · 2017
Summary
Alzheimer's disease (AD), the main cause of dementia observed in the elderly population, is a genetically complex disease. For familial early onset AD type, there are more than 100 mutations, which are rare and highly penetrating, identified in three genes (APP, PSEN1, PSEN2). In the common late onset AD type, the apolipoprotein E (APOE) gene stands out for the increased susceptibility to AD. But; APOE gene mutations do not explain all the genetic factors causing the disease. Apart from this gene, there are other genetic factors investigated in relation to the AD. One of them is the 44-bp indel polymorphism detected in the ABCA7 gene. In literature, this deletion mutation was detected at a high frequency among American citizens of African-origin with AD. In this project, the presence and frequency of ABCA7 gene 44-bp indel polymorphism was investigated among sampled AD patients (n=50) and control individuals (n=25). The AD patients were all diagnosed with Alzheimer's disease based on MRI analysis. Results revealed that, all the samples were homozygotes for the ABCA7 gene wild-type allele. There was only one sample (AD patient), who was heterozygote for this allele carrying both the wild-type allele and the allele with the 44-bp deletion mutation. When we look at this individual's family history, it was revealed that they have immigrated from Africa to settle in Turkey. This indel mutation was detected in African descent American individuals with AD for the first time in the literature. Diseases, vectors and environmental conditions in African geography can put pressure on different genes compared to other geographic regions. When we look at the findings in the literature and our results, no support has been obtained to support the relationship of AD with the ABCA7 gene 44-bp deletion mutation. The frequency of the 44-bp deletion mutation in the ABCA7 gene might have been increased in the African populations’ genetic pool regardless of AD, resulting from selective sweep or genetic hitchhiking, while some other genes are being selected due to independent factors.