1. The CDC2 I-G-T haplotype associated with the APOE epsilon4 allele increases the risk of sporadic Alzheimer's disease in Sicily.
- Author
-
Bosco P, Caraci F, Copani A, Spada RS, Sortino MA, Salluzzo R, Salemi M, Nicoletti F, and Ferri R
- Subjects
- Female, Gene Frequency, Genotype, Humans, Male, Polymerase Chain Reaction, Polymorphism, Genetic, Risk Factors, Sicily epidemiology, Alzheimer Disease genetics, Apolipoprotein E4 genetics, Cell Cycle Proteins genetics, Genetic Predisposition to Disease, Haplotypes
- Abstract
The cell division cycle 2 (CDC2) gene is a candidate susceptibility gene for Alzheimer's disease (AD). We investigated the CDC2 genotype, and allele and haplotype frequencies in AD patients and matched controls, distinguishing between apolipoprotein E (APOE) epsilon4 allele carriers and non-carriers. APOE epsilon4 is an established predictor of AD risk. APOE and CDC2 genotypes were examined in 109 sporadic AD patients and in 110 healthy age- and sex-matched controls from Sicily. The epsilon4 allele of APOE was predictive of AD risk in our study group (odds ratio: 5.37, 95% CI 2.77-10.41; P<0.0001). Genotype and allele frequencies of the three tested CDC2 polymorphisms (Ex6+7I/D, Ex7-15 G>A, Ex7-14 T>A) were not significantly different between AD patients and controls. However, a significant different distribution of a specific CDC2 haplotype (I-G-T) was found between AD patients and controls when analyzing APOE epsilon4-positive subjects (P=0.0288). Moreover, the combined presence of the I-G-T haplotype and the epsilon4 allele almost doubled the risk of AD (odds ratio: 10.09, 95% CI 3.88-26.25; P<0.0001) compared to carriers of epsilon4 alone. This study suggests that the I-G-T haplotype of the CDC2 gene increases the risk of AD in APOE epsilon4 carriers.
- Published
- 2007
- Full Text
- View/download PDF