Association of NOTCH4 and ACHE gene polymorphism in Alzheimer’s disease of Gujarat cohort

Abstract

BackgroundAlzheimer's Disease (AD) is the most common form of dementia, affecting cognitive and behavioral functions. AD is a complex disease resulting from the modest effect of gene interaction and environmental factors, as a result of which the exact pathogenesis is still unknown. AimThe aim of the present study was to investigate the association between variants of 98 targeted genes with Alzheimer's disease phenotype. MethodA total of 98 genes from 32 AD cases and 11 controls were genotyped using the Haloplex target enrichment method and the PCR-RFLP approach.Association analysis was performed using the PLINK tool to identify the variant significantly associated with AD. Functional enrichment analysis and network analysis was performed using ClueGo and String database respectively. The Expression Quantitative Trait Loci (eQTL) analysis using the Genotype Tissue Expression (GTEx) dataset to explore the possible implication of the variant on the expression of one or more genes in different brain regions and whole blood. ResultAssociation analysis showed significant association of 19 variant assigned to 16 genes with Alzheimer’s with p-value < 0.05 with rs367398/NOTCH4 only variant that passed multiple test corrections. Functional enrichment analysis showed association of these genes with AD. ClueGo and network analysis utilizing the String database suggested that genes are directly and indirectly linked to the AD pathogenesis. eQTL analysis revealed that the rs367398/NOTCH4 and rs1799806/ACHE variant showed significant eQTL for the neighbouring genes. ConclusionThe present study showed the possible role of 16 genes in AD pathogenesis, especially highlighting the role of rs367398/NOTCH4 and rs1799806/ACHE. However further investigation with large cohort is required to study and validate the implication of these variants in the AD pathogenesis.