Association of insulin-like growth factor-1 receptor polymorphism in dementia

There is an increasing interest in how oxidative stress can cause cells to go into apoptosis in both normal ageing and in neurodegenerative disorders. Previous research has implicated insulin-like growth factor-1 (IGF-1) as being involved in the pathogenesis in Alzheimer's disease (AD) by protecting the neurons through reducing neuronal susceptibility to oxidative stress. IGF-1 receptor (IGF-1R) polymorphisms alter cerebral and systemic levels of IGF-1 and may alter the function of the receptor. We genotyped the IGF-1R gene by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to assess whether this gene polymorphism can be linked to dementia. We used leukocyte DNA from 72 patients with AD, 75 patients with vascular dementia (VaD), 14 patients with mixed dementia (AD+VaD), and a control group consisting of 209 individuals without a history of progressive neurological disorders. Analysis of gene frequency for gender revealed a significant difference between female VaD patients and female controls carrying at least one A allele (OR = 1.8, CI 95% 1.1-2.9, p = 0.02), but not for male patients. In addition, we found a strong tendency to a difference between all cases of female dementia patients and controls carrying the A allele (OR = 1.5, CI 95% 0.99-2.2, p = 0.054). Our results suggest that the A allele of IGF-1R may be involved in the pathogenesis of VaD in females. Copyright © 2006 S. Karger AG.