title: PIN1 promoter polymorphisms are associated with Alzheimer's disease.
abstract: In our study, we analyzed the coding and promoter regions of the PIN1 gene in a group of 111 Alzheimer's disease (AD) patients looking for a possible genotype-phenotype correlation. The presence of SNPs - which could affect and modify the clinical phenotype of AD patients was also investigated. We identified two single nucleotide polymorphisms (SNPs) at positions -842 (G-->C) and -667 (C-->T) in the promoter region of the PIN1 gene. Our results evidenced a significantly higher percentage of -842C allele carriers in AD subjects with respect to healthy controls. We found that this allele significantly raised the risk of developing AD (OR 3.044, CI 1.42-6.52). The -842 and -667 SNPs were in linkage disequilibrium and combined to form haplotypes. The CC haplotype conferred a higher risk of developing AD (OR 2.95, confidence interval 1.31-6.82). Finally, protein expression analyses revealed that subjects carrying the -842 CC genotype or the CC haplotype showed reduced levels of the PIN1 protein in peripheral mononuclear cells.
authors.affiliation: Department of Reproductive and Developmental Sciences, University of Trieste, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Segat
authors.forename: A
authors.initials: A
authors.lastname: Pontillo
authors.forename: G
authors.initials: G
authors.lastname: Annoni
authors.forename: D
authors.initials: D
authors.lastname: Trabattoni
authors.forename: C
authors.initials: C
authors.lastname: Vergani
authors.forename: M
authors.initials: M
authors.lastname: Clerici
authors.forename: B
authors.initials: B
authors.lastname: Arosio
authors.forename: S
authors.initials: S
authors.lastname: Crovella
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase