Investigating the Potential Impact of Variables in nontranslocational Regions of key Genes in Amyotrophic lateral sclerosis and Their Relationship with Disease Progression
Investigating the Potential Impact of Variables in nontranslocational Regions of key Genes in Amyotrophic lateral sclerosis and Their Relationship with Disease Progression
Alireza Nasr Esfahani,1,*Setare Samizade,2
1. Islamic Azad University, Department of Biology, Falavarjan Branch, Isfahan, Iran 2. Islamic Azad University, Department of Biology, Falavarjan Branch, Isfahan, Iran
Introduction: Amyotrophic lateral sclerosis (ALS) is an irreversible neurodegenerative
disorder characterized by the selective and progressive loss of upper and lower motor neurons
of the cerebral cortex, brainstem, and spinal cord. Leptin has been suggested to play a role in
amyotrophic lateral sclerosis (ALS), a fatal progressive neurodegenerative disease. This
adipokine has previously been shown to be associated with a lower risk of ALS and to confer
a survival advantage in ALS patients. Genome-wide association studies (GWAS) are the most
common approach to detecting relationships between genetic variants (frequently, a
singlenucleotide polymorphism—SNP) and disease occurrence. One of the possible cause is
single-nucleotide polymorphisms (SNP) in the untranslated region (UTR) of active genes in
CNS.
Methods: The literature review was used to collecting the ALS -related most susceptible
genes. Then, using miRNASNP database, the miRNA-related SNPs located on the 3ʼUTR of
genes were identified. Finally, the pathway enrichment analysis was performed by the KEGG
database.
Results: Our results demonstrated that plasminogen activator inhibitor type 1 (PAI1), gastric inhibitory peptide (GIP), glucagon-like peptide 1 (GLP-1), insulin and glucagon are
critical genes in ALS progression, in which on their 3ʼUTR there are some high-frequency
polymorphisms located within the miRNAs target site. These variants may result in an
expression blockage of mentioned genes during ALS. The pathway analysis resulted to found
that miRNAs in genes (PAI-1 rs1436918 G/A with miRNA: hsa-miR-499a-3p, GIP
rs16984239 C/T with miRNA: hsa-miR-551b-5p/3p, GLP-1 rs10459680 T/G with miRNA:
hsa-miR-3126-5p/3p) have interfering effects on same of the cancers and hepatitis genes.
Conclusion: Upon the fact that any changes in SNP alleles cause mutations in the vital genes
for the normal functioning of the nervous system, it can be stated that these SNPs may play
role in development and progression of ALS. These results may open the new route to develop
molecular controlling of Cancer, Hepatitis and ALS in future.