BMC medical genetics · 2009
PIN1 gene variants in Alzheimer's disease.
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Maruszak Aleksandra, Safranow Krzysztof, Gustaw Katarzyna, Kijanowska-Haładyna Beata, Jakubowska Katarzyna, Olszewska Maria, Styczyńska Maria, Berdyński Mariusz, Tysarowski Andrzej, Chlubek Dariusz, Siedlecki Janusz, Barcikowska Maria, Zekanowski Cezary
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAge of OnsetAgedAged, 80 and overAlzheimer DiseaseCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenetic VariationHaplotypesHumansLinkage DisequilibriumMaleMiddle AgedNIMA-Interacting Peptidylprolyl IsomerasePeptidylprolyl IsomerasePolymorphism, Single NucleotidePromoter Regions, Genetic