title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warszawa, Poland. ola.maruszak@cmdik.pan.pl
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Maruszak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Safranow
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gustaw
authors.forename: Beata
authors.initials: B
authors.lastname: Kijanowska-Haładyna
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jakubowska
authors.forename: Maria
authors.initials: M
authors.lastname: Olszewska
authors.forename: Maria
authors.initials: M
authors.lastname: Styczyńska
authors.forename: Mariusz
authors.initials: M
authors.lastname: Berdyński
authors.forename: Andrzej
authors.initials: A
authors.lastname: Tysarowski
authors.forename: Dariusz
authors.initials: D
authors.lastname: Chlubek
authors.forename: Janusz
authors.initials: J
authors.lastname: Siedlecki
authors.forename: Maria
authors.initials: M
authors.lastname: Barcikowska
authors.forename: Cezary
authors.initials: C
authors.lastname: Zekanowski
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase