PIN1 promoter polymorphisms are associated with Alzheimer's disease

• Published in: Neurobiology of aging 2007-01, Vol.28 (1), p.69-74
• Main Authors: Segat, L, Pontillo, A, Annoni, G, Trabattoni, D, Vergani, C, Clerici, M, Arosio, B, Crovella, S
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer's disease; Biological and medical sciences; Biomarkers - analysis; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Development. Senescence. Regeneration. Transplantation; DNA Mutational Analysis - methods; Female; Fundamental and applied biological sciences. Psychology; Genetic polymorphisms; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genetic Testing - methods; Genotype; Genotype–phenotype correlation; Heterozygote; Humans; Incidence; Internal Medicine; Italy - epidemiology; Male; Medical sciences; Neurofibrillary degeneration; Neurology; NIMA-Interacting Peptidylprolyl Isomerase; Peptidylprolyl Isomerase - genetics; PIN1; Polymorphism, Single Nucleotide - genetics; Promoter Regions, Genetic - genetics; Risk Assessment - methods; Risk Factors; Vertebrates: nervous system and sense organs
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2005.11.009

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.