title: Interaction between poly(ADP-ribose) polymerase 1 and interleukin 1A genes is associated with Alzheimer's disease risk.
abstract: 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.
authors.affiliation: Neurology Service, Marqués de Valdecilla University Hospital, University of Cantabria, Santander, Spain.
authors.forename: Jon
authors.initials: J
authors.lastname: Infante
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
authors.forename: Ignacio
authors.initials: I
authors.lastname: Mateo
authors.forename: Eloy
authors.initials: E
authors.lastname: Rodríguez-Rodríguez
authors.forename: Coro
authors.initials: C
authors.lastname: Sánchez-Quintana
authors.forename: Pascual
authors.initials: P
authors.lastname: Sánchez-Juan
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Viadero
authors.forename: Nicolás
authors.initials: N
authors.lastname: Peña
authors.forename: José
authors.initials: J
authors.lastname: Berciano
authors.forename: Onofre
authors.initials: O
authors.lastname: Combarros
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D011110:Polymorphism, Genetic; D012016:Reference Values; D012307:Risk Factors
chemical_list: D053582:Interleukin-1alpha; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases