title: Association analysis of the paraoxonase-1 gene with Alzheimer's disease.
abstract: Genetic variants in the paraoxonase (PON) gene cluster, particularly a single C/T promoter polymorphism (rs 705381) in the PON-1 gene, have recently been associated with Alzheimer's disease (AD). The T allele, in particular, presents an increased risk for the development of AD. Here, we investigate the potential role of this polymorphism in an Italian case-control population consisting of 306 sporadic AD patients and 275 controls, and also evaluate a possible interaction with the ApoE genotype. No association between the PON-1 polymorphism and AD was observed. The T allele frequency was slightly over-represented in AD patients compared to the controls, but this was far from being statistically significant. Our sample was evaluated to have 97.3% power to detect an OR of 2.0 (64.3% power with OR=1.5) at an alpha level of 0.05. No evidence of an interaction between the T risk-allele and the ApoE epsilon4 allele status and no effect of the PON-1 polymorphism on age at onset was detected. Our results do not support other studies indicating that the PON-1 promoter polymorphism plays a major role in AD, suggesting that other large studies are necessary to further elucidate the effect of PON on the development of the disease in the general population.
authors.affiliation: Department of Neurological and Psychiatric Sciences, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy. elena.cellini@unifi.it
authors.forename: Elena
authors.initials: E
authors.lastname: Cellini
authors.forename: Andrea
authors.initials: A
authors.lastname: Tedde
authors.forename: Silvia
authors.initials: S
authors.lastname: Bagnoli
authors.forename: Benedetta
authors.initials: B
authors.lastname: Nacmias
authors.forename: Silvia
authors.initials: S
authors.lastname: Piacentini
authors.forename: Valentina
authors.initials: V
authors.lastname: Bessi
authors.forename: Laura
authors.initials: L
authors.lastname: Bracco
authors.forename: Sandro
authors.initials: S
authors.lastname: Sorbi
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D053327:Apolipoprotein E4; D012333:RNA, Messenger; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human