The CDC2 I-G-T haplotype associated with the APOE ε4 allele increases the risk of sporadic Alzheimer's disease in Sicily

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) epsilon 4 allele carriers and non-carriers. APOE epsilon 4 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 e4 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 epsilon 4-positive subjects (P = 0.0288). Moreover, the combined presence of the I-G-T haplotype and the epsilon 4 allele almost doubled the risk of AD (odds ratio: 10.09, 95% CI 3.88-26.25; P < 0.0001) compared to carriers of e4 alone. This study suggests that the I-G-T haplotype of the CDC2 gene increases the risk of AD in APOE e4 carriers. (C) 2007 Elsevier Ireland Ltd. All rights reserved.