A Novel Association of Polymorphism in the ITGA4 Gene Encoding the VLA-4 α4 Subunit with Increased Risk of Alzheimer’s Disease
Alzheimer’s disease (AD) is the most prevalent cause of dementia in elderly people worldwide. Many studies support the hypothesis that the inflammation of the CNS contributes to the neurodegeneration and disease progression. The integrin molecule α4β1, also known as very late antigen 4 (VLA-4), belo...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2018/7623823 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832550032455237632 |
|---|---|
| author | Vladimira Durmanova Zuzana Parnicka Juraj Javor Gabriel Minarik Lubomir Vrazda Barbora Vaseckova Karin Gmitterova Maria Kralova Jan Pecenak Peter Filipcik Ivana Shawkatova |
| author_facet | Vladimira Durmanova Zuzana Parnicka Juraj Javor Gabriel Minarik Lubomir Vrazda Barbora Vaseckova Karin Gmitterova Maria Kralova Jan Pecenak Peter Filipcik Ivana Shawkatova |
| author_sort | Vladimira Durmanova |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most prevalent cause of dementia in elderly people worldwide. Many studies support the hypothesis that the inflammation of the CNS contributes to the neurodegeneration and disease progression. The integrin molecule α4β1, also known as very late antigen 4 (VLA-4), belongs to adhesion molecules that activate the inflammatory process through the migration of immune cells into the CNS. Therefore, the objective of our study was to analyze the association between two polymorphisms located in the ITGA4 gene encoding the α4 subunit of VLA-4 and the risk of AD. 104 late-onset AD patients and 206 control subjects from Slovakia were genotyped for ITGA4 gene SNP polymorphism rs113276800 (−269C/A) and rs1143676 (+3061A/G). The same study cohorts were also genotyped for the APOE-ε4, which is a known genetic factor associated with increased risk of AD developing. ITGA4 polymorphism analysis revealed significantly higher frequency of the +3061AG carriers in AD group compared to the controls (P≤0.05). Following the APOE-ε4 stratification of study groups, the association remained significant only in APOE-ε4 noncarriers. Our study suggests a novel association of ITGA4 +3061A/G polymorphism with AD and its possible contribution to the disease pathology. |
| format | Article |
| id | doaj-art-d11a9d69bf074514b399d87d516e380c |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-d11a9d69bf074514b399d87d516e380c2025-02-03T06:07:55ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/76238237623823A Novel Association of Polymorphism in the ITGA4 Gene Encoding the VLA-4 α4 Subunit with Increased Risk of Alzheimer’s DiseaseVladimira Durmanova0Zuzana Parnicka1Juraj Javor2Gabriel Minarik3Lubomir Vrazda4Barbora Vaseckova5Karin Gmitterova6Maria Kralova7Jan Pecenak8Peter Filipcik9Ivana Shawkatova10Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, SlovakiaInstitute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, SlovakiaInstitute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, SlovakiaDepartment of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava, Bratislava, SlovakiaCare Center Centrum Memory, Bratislava, SlovakiaPsychiatry Outpatient Clinics, University Hospital and Policlinic The Brothers of Saint John of God in Bratislava, Bratislava, Slovakia2nd Department of Neurology, Faculty of Medicine, Comenius University in Bratislava and University Hospital, Bratislava, SlovakiaClinic of Psychiatry, Faculty of Medicine, Comenius University in Bratislava and University Hospital, Bratislava, SlovakiaClinic of Psychiatry, Faculty of Medicine, Comenius University in Bratislava and University Hospital, Bratislava, SlovakiaInstitute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, SlovakiaInstitute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, SlovakiaAlzheimer’s disease (AD) is the most prevalent cause of dementia in elderly people worldwide. Many studies support the hypothesis that the inflammation of the CNS contributes to the neurodegeneration and disease progression. The integrin molecule α4β1, also known as very late antigen 4 (VLA-4), belongs to adhesion molecules that activate the inflammatory process through the migration of immune cells into the CNS. Therefore, the objective of our study was to analyze the association between two polymorphisms located in the ITGA4 gene encoding the α4 subunit of VLA-4 and the risk of AD. 104 late-onset AD patients and 206 control subjects from Slovakia were genotyped for ITGA4 gene SNP polymorphism rs113276800 (−269C/A) and rs1143676 (+3061A/G). The same study cohorts were also genotyped for the APOE-ε4, which is a known genetic factor associated with increased risk of AD developing. ITGA4 polymorphism analysis revealed significantly higher frequency of the +3061AG carriers in AD group compared to the controls (P≤0.05). Following the APOE-ε4 stratification of study groups, the association remained significant only in APOE-ε4 noncarriers. Our study suggests a novel association of ITGA4 +3061A/G polymorphism with AD and its possible contribution to the disease pathology.http://dx.doi.org/10.1155/2018/7623823 |
| spellingShingle | Vladimira Durmanova Zuzana Parnicka Juraj Javor Gabriel Minarik Lubomir Vrazda Barbora Vaseckova Karin Gmitterova Maria Kralova Jan Pecenak Peter Filipcik Ivana Shawkatova A Novel Association of Polymorphism in the ITGA4 Gene Encoding the VLA-4 α4 Subunit with Increased Risk of Alzheimer’s Disease Mediators of Inflammation |
| title | A Novel Association of Polymorphism in the ITGA4 Gene Encoding the VLA-4 α4 Subunit with Increased Risk of Alzheimer’s Disease |
| title_full | A Novel Association of Polymorphism in the ITGA4 Gene Encoding the VLA-4 α4 Subunit with Increased Risk of Alzheimer’s Disease |
| title_fullStr | A Novel Association of Polymorphism in the ITGA4 Gene Encoding the VLA-4 α4 Subunit with Increased Risk of Alzheimer’s Disease |
| title_full_unstemmed | A Novel Association of Polymorphism in the ITGA4 Gene Encoding the VLA-4 α4 Subunit with Increased Risk of Alzheimer’s Disease |
| title_short | A Novel Association of Polymorphism in the ITGA4 Gene Encoding the VLA-4 α4 Subunit with Increased Risk of Alzheimer’s Disease |
| title_sort | novel association of polymorphism in the itga4 gene encoding the vla 4 α4 subunit with increased risk of alzheimer s disease |
| url | http://dx.doi.org/10.1155/2018/7623823 |
| work_keys_str_mv | AT vladimiradurmanova anovelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT zuzanaparnicka anovelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT jurajjavor anovelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT gabrielminarik anovelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT lubomirvrazda anovelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT barboravaseckova anovelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT karingmitterova anovelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT mariakralova anovelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT janpecenak anovelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT peterfilipcik anovelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT ivanashawkatova anovelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT vladimiradurmanova novelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT zuzanaparnicka novelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT jurajjavor novelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT gabrielminarik novelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT lubomirvrazda novelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT barboravaseckova novelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT karingmitterova novelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT mariakralova novelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT janpecenak novelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT peterfilipcik novelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease AT ivanashawkatova novelassociationofpolymorphismintheitga4geneencodingthevla4a4subunitwithincreasedriskofalzheimersdisease |