A Novel Association of Polymorphism in theITGA4Gene Encoding the VLA-4α4 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 moleculeα4β1, 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 theITGA4gene encoding theα4 subunit of VLA-4 and the risk of AD. 104 late-onset AD patients and 206 control subjects from Slovakia were genotyped forITGA4gene SNP polymorphism rs113276800 (−269C/A) and rs1143676 (+3061A/G). The same study cohorts were also genotyped for theAPOE-ε4, which is a known genetic factor associated with increased risk of AD developing.ITGA4polymorphism analysis revealed significantly higher frequency of the +3061AG carriers in AD group compared to the controls (P≤0.05). Following theAPOE-ε4 stratification of study groups, the association remained significant only inAPOE-ε4 noncarriers. Our study suggests a novel association ofITGA4+3061A/G polymorphism with AD and its possible contribution to the disease pathology.