PIN1 promoter polymorphisms are associated with Alzheimerʹs disease

In our study, we analyzed the coding and promoter regions of the PIN1 gene in a group of 111 Alzheimerʹs 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.