PIN1 gene variants in Alzheimer's disease.

Abstract

BACKGROUND:

Peptidyl-prolyl isomerase, NIMA-interacting 1 (PIN1) plays a significant role in the brain and is implicated in numerous cellular processes related to Alzheimer's disease (AD) and other neurodegenerative conditions. There are confounding results concerning PIN1 activity in AD brains. Also PIN1 genetic variation was inconsistently associated with AD risk.

METHODS:

We performed analysis of coding and promoter regions of PIN1 in early- and late-onset AD and frontotemporal dementia (FTD) patients in comparison with healthy controls.

RESULTS:

Analysis of eighteen PIN1 common polymorphisms and their haplotypes in EOAD, LOAD and FTD individuals in comparison with the control group did not reveal their contribution to disease risk.In six unrelated familial AD patients four novel PIN1 sequence variants were detected. c.58+64C>T substitution that was identified in three patients, was located in an alternative exon. In silico analysis suggested that this variant highly increases a potential affinity for a splicing factor and introduces two intronic splicing enhancers. In the peripheral leukocytes of one living patient carrying the variant, a 2.82 fold decrease in PIN1 expression was observed.

CONCLUSION:

Our data does not support the role of PIN1 common polymorphisms as AD risk factor. However, we suggest that the identified rare sequence variants could be directly connected with AD pathology, influencing PIN1 splicing and/or expression.

• Authors: Aleksandra Maruszak, Krzysztof Safranow, Katarzyna Gustaw, Beata Kijanowska-Haładyna, Katarzyna Jakubowska, Maria Olszewska, Maria Styczyńska, Mariusz Berdyński, Andrzej Tysarowski, Dariusz Chlubek, Janusz Siedlecki, Maria Barcikowska, Cezary Zekanowski
• Journal: BMC medical genetics (BMC Med Genet) Vol. 10 Pg. 115 (Nov 12 2009) ISSN: 1471-2350 [Electronic] England
• PMID: 19909517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NIMA-Interacting Peptidylprolyl Isomerase
• PIN1 protein, human
• Peptidylprolyl Isomerase

Topics

• Adult
• Age of Onset
• Aged
• Aged, 80 and over
• Alzheimer Disease (genetics)
• Case-Control Studies
• Female
• Genetic Predisposition to Disease
• Genetic Variation
• Haplotypes
• Humans
• Linkage Disequilibrium
• Male
• Middle Aged
• NIMA-Interacting Peptidylprolyl Isomerase
• Peptidylprolyl Isomerase (genetics)
• Polymorphism, Single Nucleotide
• Promoter Regions, Genetic