PIN-1 promoter polymorphisms in mild cognitive impairment and susceptibility to Alzheimer's disease: a preliminary report.
OBJECTIVE
Peptydil prolyl cis-trans isomerase (PIN-1), which specifically regulates the conformational changes following phosphorylation of several proteins, targets the inactive hyper-phosphorylated tau on the Thr231-Pro motif and directly restores its biological function. Interestingly, PIN-1 is oxidatively inhibited not only in Alzheimer's disease brain but also in the hippocampi of mild cognitive impairment (MCI) subjects. The PIN-1 gene is characterized by two single nucleotide polymorphisms (SNPs) in the promoter region which are associated with the risk of Alzheimer's disease. The aim of this study was to analyse the genotype and allele distributions of these PIN-1 SNPs in MCI subjects diagnosed respectively as amnestic MCI (a-MCI) and multiple impaired cognitive domains (mcd-MCI) on the basis of cognitive features.


METHODS
-667 T/C and -842 C/G SNPs were genotyped by polymerase chain reaction (PCR) amplification and direct sequencing in 43 MCI subjects, with the intention of comparing -667 and -842 SNP frequencies with those previously described in 111 Alzheimer's disease patients (AD) and 73 healthy controls (HC).


RESULTS
The allele frequencies of the -842 C/G SNP in a-MCI subjects are similar to those of AD subjects, while those of mcd-MCI are comparable to HC (G allele 83% in both a-MCI and AD; 95% and 94% in mcd-MCI and HC, respectively). A similar trend is also observed in -842 C/G genotypes.


CONCLUSIONS
Since a-MCI is thought to be the preclinical form of AD, the similar genotype distribution of -842 SNP in AD and a-MCI, but not in mcd-MCI, suggests that it is potentially involved in the conversion of a-MCI to AD. In conclusion, these findings support the theory that polymorphisms of the PIN-1 gene can affect neurodegeneration and its clinical progression.
Arosio
Beatrice
B
Geriatric Unit, Department of Internal Medicine, University of Milan, Ospedale Maggiore Policlinico, IRCCS Milano, Via Pace 9, Milan, Italy. beatrice.arosio@unimi.it
Segat
Ludovica
L
Milanese
Michele
M
Galimberti
Lorenza
L
Calabresi
Carmen
C
Zanetti
Mariella
M
Trabattoni
Daria
D
Annoni
Giorgio
G
Crovella
Sergio
S
Vergani
Carlo
C
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase