The CDC2 I-G-T haplotype associated with the APOE 4 allele increases the risk of sporadic Alzheimer's disease in Sicily

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• 作者：Paolo Bosco ; Filippo Caraci ; Agata Copani ; Rosario S. Spada ; Maria Angela Sortino ; Roberto Salluzzo ; Michele Salemi ; Ferdin ; o Nicoletti ; Raffaele Ferri
• 关键词：Alzheimer's disease ; APOE ; cdc2 ; Cell cycle ; Genetic polymorphism ; Risk factor
• 刊名：Neuroscience Letters
• 出版年：2007
• 出版时间：4 June 2007
• 年：2007
• 卷：419
• 期：3
• 页码：195-198
• 全文大小：114 K

文摘

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) 4 allele carriers and non-carriers. APOE 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 4 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 4-positive subjects (P = 0.0288). Moreover, the combined presence of the I-G-T haplotype and the 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 4 alone. This study suggests that the I-G-T haplotype of the CDC2 gene increases the risk of AD in APOE 4 carriers.