Association of Insulin Receptor Substrate-1 Gene Polymorphism (rs1801278) with Alzheimer's Disease

Abstract

Background: Alzheimer's disease (AD) is the most common form of dementia. AD is also the leading cause of morbidity and mortality due to dementia worldwide. It has been shown that AD is associated with type 2 diabetes mellitus (T2DM) and brain insulin resistance. Rs1801278 is a polymorphism in insulin receptor substrate-1 (IRS-1) gene which changes the amino acid Arg972. This polymorphism has been found to be associated with susceptibility to AD in some populations. Objective: In the present study, our aim was to investigate the association of Arg972 IRS-1 (rs1801278) gene polymorphism and late-onset Alzheimer's disease (LOAD) in an Iranian population. Methods: In this case-control study, 150 patients with LOAD and 150 unrelated healthy controls were recruited. Polymerase chain reaction (PCR) was performed to amplify a DNA segment of 263 base-pair (bp) length containing the single nucleotide polymorphism (SNP). The PCR product was then incubated with MvaI restriction enzyme to undergo enzymatic cleavage. Electrophoresis was thereafter carried out using agarose gel and DNA safe stain. The gel was ultimately visualized under a UV trans-illuminator. Allelic and genotypic frequencies were then compared. Results: A allele (mutant) of the gene was significantly associated with the risk of AD after adjustment for sex and age (p = 0.04, adjusted OR:1.77, 95% CI:1.00-3.11). Only AA genotype (mutant homozygote) was significantly associated with the risk of AD after adjustment for sex and age (p = 0.01, adjusted OR:2.39, 95% CI:1.22-4.66). Conclusion: SNP rs1801278 is significantly associated with the risk of developing AD in the studied Iranian population.