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Allied Journal of Medical Research
|
Volume 2
Page 46
allied
academies
CANCER THERAPY AND ONCOLOGY
NEUROLOGY AND BRAIN DISORDERS
&
International Conference on
International Conference on
J u n e 2 1 - 2 2 , 2 0 1 8 | O s a k a , J a p a n
Joint Event on
DEMENTIA OF ALZHEIMER’S TYPE AMONG ARAB POPULATIONS:
GENETICS AND EPIDEMIOLOGICAL STUDIES
Bowirrat Abdalla
EMMS Hospital, Nazareth Hospital, Israel
Introduction:
Neurodegenerative disorders, Primarily, are multifactorial diseases characterized by chronic and progressive
loss of neurons in discrete areas of the brain, causing debilitating symptoms and globally decreasing cognitive function
such as dementia, loss of memory, loss of sensory or motor capability, decreased overall quality of life and well-being,
disability, and eventually, premature death.
Objective:
To study the genetic and environmental risk factors and the prevalence of dementia of the Alzheimer type (DAT)
among the elderly in an Arab community in Israel.
Material and Methods:
Epidemiological and genetic studies of dementia have rarely been reported in an Arab population.
Alzheimer disease (AD [MIM #104300]) is a progressive, neurodegenerative disease characterized clinically by gradual loss
of memory and pathologically by neurofibrillary tangles and amyloid plaques in the brain. We have observed an unusually
high prevalence of dementia of the Alzheimer type (DAT) inWadi Ara, an inbred Arab community in northern Israel comprising
∼850 persons over the age of 60 years. Apolipoprotein E (APOE- ε4), has been established as a strong susceptibility marker
that accounts for nearly 30% of the risk in late-onset AD.
Results:
Remarkably, in our study DAT is not associated with APOE because the frequency of the ɛ4 allele is very low in
both nondemented (2.4%) and demented elders (3.6%). We also map chromosomal loci contributing to DAT susceptibility;
we conducted a 10 cM scan in a series of twenty cases and twenty controls selected from one hamula. Markers from 18
chromosomal regions showed significant allelic association with DAT (P<0.05). Locations on chromosomes 2, 9 and 10
remained significant after testing additional affected and non-demented individuals. Significant associations were also
observed for markers on chromosome 12, which overlap with a locus implicated in previous genome scans. Additionally,
several lines of evidence support for a role of angiotensin converting enzyme (ACE) in Alzheimer disease (AD). Most genetic
studies have focused on an Alu insertion/deletion (I/D) polymorphism in the ACE gene (DCP1) and have yielded conflicting
results. We evaluated the association between 15 (SNPs) in DCP1, including the I/D variant, and AD in a sample of 92
patients with AD and 166 non-demented controls from an inbred Israeli Arab community.Although there was no evidence
for association between AD and I/D, we observed significant association with SNPs rs4343 (P= .00001) and rs4351 (P=.01).
Conclusion:
In Wadi Ara the high prevalence may be due to a founder effect enhanced by consanguinity, which make this
population attractive for investigating DATsusceptibility recessive genes; thus, a specific disease susceptibility allelemay be
overrepresented in cognitively impaired subjects compared with cognitively healthy residents. Other two main conclusions
can be drawn from the genome-wide linkage and linkage disequilibrium (LD) studies. Firstly, multiple genes are involved in
DAT. Secondly, there is a high level of consistency among linkage and association studies regarding the general location of
putative AD genes. However, the general location of putative AD genes on a given chromosome covers a broad region, which
may contain several genes.
BOWIRRAT@bezeqint.netAllied J Med Res 2018, Volume 2