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Vol. 23, No. 4, 2007
Issue release date: March 2007
Dement Geriatr Cogn Disord 2007;23:215–218

Interaction between Poly(ADP-Ribose) Polymerase 1 and Interleukin 1A Genes Is Associated with Alzheimer’s Disease Risk

Infante J. · Llorca J. · Mateo I. · Rodríguez-Rodríguez E. · Sánchez-Quintana C. · Sánchez-Juan P. · Fernández-Viadero C. · Peña N. · Berciano J. · Combarros O.
aNeurology Service, Marqués de Valdecilla University Hospital, University of Cantabria, bDivision of Preventive Medicine, University of Cantabria School of Medicine, and cRTE Santander, Consejería de Sanidad, Santander, Spain

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Excessive release of proinflammatory cytokines by activated microglia surrounding senile plaques might contribute to the neurodegeneration associated with Alzheimer’s disease (AD). Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear protein recently implicated in the initial inflammatory response by modulating expression of inflammation-related genes, like interleukin 1 (IL-1). As PARP-1 overactivity has been shown in the AD brain, we tested the hypothesis that the PARP-1 –410 and –1672 polymorphisms would predispose people to AD due to overexpression of the PARP-1 gene, independently or in concert with the proinflammatory IL-1A –889 polymorphism. So, we performed a case-control study in 263 Spanish AD patients and 293 healthy controls. PARP-1 –410 and PARP-1 –1672 haplotypes were associated with an increased risk for AD (global haplotype association p value = 0.019), and, in addition, PARP-1 haplotypes increased the risk of AD by interaction with the IL-1A –889 allele 2.

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    External Resources

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