IRS gene polymorphisms in Turkish patients with late-onset Alzheimer's disease

Factors that cause changes in insulin signaling in the brain are thought to affect the synaptic plasticity and accelerate the process of brain aging and neurodegeneration. Insulin receptor substrate (IRS) molecules are key mediators in insulin signaling. The aim of the current study is to determine whether there is an association between IRS gene polymorphisms, which are critical for insulin signaling, and the late-onset Alzheimer's disease in Turkish patients.

Demographic and clinical characteristics of 115 patients with late-onset Alzheimer's disease (age of onset ≥ 65 years) and 107 age-matched control subjects were obtained. DNAs were isolated from patient and control groups, IRS-1 and IRS-2 gene polymorphisms were investigated and genotyped according to the PCR-RFLP method. No statistically significant difference was observed in the genotypes for IRS-1 Gly972Arg (rs1801278) (p = 0.499) and IRS-2 Gly1057Asp (rs1805097) polymorphism between late-onset Alzheimer's disease patients and controls (p = 0.658). However, when the compliance of IRS-2 polymorphism with Hardy- Weinberg distribution was tested, in the case-control comparison, G allele frequency of IRS-2 polymorphisms was significantly higher in the patient population than in the control group in the Turkish population of the Thrace region.

Despite the potential role of insulin resistance and hyperinsulinemia in the development of Alzheimer's disease, we did not find any association between polymorphism of the IRS-1 and IRS-2 genes and late-onset Alzheimer's disease. However, compared to the healthy subjects, Gly/Gly genotypes and the G allele in the IRS-2 were significantly more frequent in patients with late-onset Alzheimer's disease.