title: The CDC2 I-G-T haplotype associated with the APOE epsilon4 allele increases the risk of sporadic Alzheimer's disease in Sicily.
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.
authors.affiliation: IRCCS Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, 94018 Troina, Enna, Italy. pbosco@oasi.en.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Bosco
authors.forename: Filippo
authors.initials: F
authors.lastname: Caraci
authors.forename: Agata
authors.initials: A
authors.lastname: Copani
authors.forename: Rosario S
authors.initials: RS
authors.lastname: Spada
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Sortino
authors.forename: Roberto
authors.initials: R
authors.lastname: Salluzzo
authors.forename: Michele
authors.initials: M
authors.lastname: Salemi
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferri
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012802:Sicily / Q000453:epidemiology
chemical_list: D053327:Apolipoprotein E4; D018797:Cell Cycle Proteins