Two recently described polymorphisms in the promoter region of the apolipoprotein E (APOE), the −491A7T and Th1/E47csT/G polymorphism, have been suggested to be associated with an increased risk for Alzheimer's disease (AD) independent from the APOE ɛ4 carrier status. We studied the association between the APOE ɛ4 polymorphism and the −491A/T and Th1E47csT/G polymorphisms in a sample of 118 healthy, non-demented controls and 239 consecutively recruited gerontopsychiatric patients diagnosed as: Alzheimer's disease (N = 89), age mild cognitive impairment (N = 32), memory complainers without any congitive deficit (N = 54) and depression/other psychiatric disorders (N = 64), to test whether the investigated polymorphisms have a high enough selectivity and specificity to distinguish between the different gerontopsychiatric disorders to differentiate AD genetically from other forms of dementia, respectively. Also a possible association with the APOE ɛ4 polymorphism was examined. We found a statistically significant association between the APOE ɛ4 allele and Alzheimer's disease (p = 0.0001) and age associated memory impairment (p = 0.006). Our study failed to show an association between the promoter polymorphisms −491A/T and Th1E47csT/G in the APOE gene and gerontopsychiatric disorders either alone or in relationship to the APOE ɛ4 polymorphism. However, if we combine our results with three previous published positive reports there seems to be an association between the −491A/T polymorphism and AD, though its size is less than found in the original publication.
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