SNP Variation in MicroRNA Biogenesis Pathway Genes as a New Innovation Strategy for Alzheimer Disease Diagnostics: A Study of 10 Candidate Genes in an Understudied Population From the Eastern Mediterranean

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dc.contributor.authorYılmaz, Şenay Görücü
dc.contributor.authorErdal, Mehmet Emin
dc.contributor.authorÖzge, Aynur Avcı
dc.contributor.authorSungur, Mehmet Ali
dc.date.accessioned2020-04-30T23:32:00Z
dc.date.available2020-04-30T23:32:00Z
dc.date.issued2016
dc.departmentDÜ, Tıp Fakültesi, Temel Tıp Bilimleri Bölümüen_US
dc.descriptionErdal, Mehmet Emin/0000-0002-6191-2930;en_US
dc.descriptionWOS: 000383914600002en_US
dc.descriptionPubMed: 26796812en_US
dc.description.abstractAlzheimer disease (AD) is a common complex neurodegenerative disorder accounting for nearly 50% to 70% of dementias worldwide. Yet the current diagnostic options for AD are limited. New diagnostic innovation strategies focusing on novel molecules and pathways are sorely needed. In this connection, microRNAs (miRNAs) are conserved small noncoding RNAs that regulate posttranscriptional gene expression and are vital for neuronal development and its functional sustainability. Conceivably, biological pathways responsible for the biogenesis of miRNAs represent a veritable set of upstream candidate genes that can be potentially associated with the AD pathophysiology. Notably, whereas functional single-nucleotide polymorphisms (SNPs) in miRNA biogenesis pathway genes have been studied in other complex diseases, surprisingly, virtually no such study has been conducted on their relevance in AD. Moreover, novel diagnostics identified in easily accessible peripheral tissues such as the whole blood samples represent the initial entry or gateway points on the biomarker discovery critical path for AD. To the best of our knowledge, we report here the first association study of functional SNPs, as measured by real-time PCR in 10 upstream candidate genes critically situated on the miRNA biogenesis pathway, in a large sample of AD patients (N=172) and healthy controls (N=109) in a hitherto understudied world population from the Mersin region of the Eastern Mediterranean. We observed a significant association between 2 candidate genes and AD, TARBP2 rs784567 genotype and AD ((2)=6.292, P=0.043), and a trend for RNASEN rs10719 genotype ((2)=4.528, P=0.104) and allele (P=0.035). Functional SNP variations in the other 8 candidate genes (DGCR8, XPO5, RAN, DICER1, AGO1, AGO2, GEMIN3, and GEMIN4) did not associate with AD in our sample. Given the putative biological importance of miRNA biogenesis pathways, these emerging data can provide a new foundation to stimulate future debate and genetic investigations of AD, focusing on new molecular mechanisms such as miRNA biogenesis, particularly in accessible peripheral tissues for novel molecular diagnostics for dementia.en_US
dc.description.sponsorshipUniversity of Mersin [BAP-SBE TB]en_US
dc.description.sponsorshipSupported by an intramural research grant from the University of Mersin [BAP-SBE TB (S.G.Y.) 2010-4].en_US
dc.identifier.doi10.1097/WAD.0000000000000135en_US
dc.identifier.endpage209en_US
dc.identifier.issn0893-0341
dc.identifier.issue3en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage203en_US
dc.identifier.urihttps://doi.org/10.1097/WAD.0000000000000135
dc.identifier.urihttps://hdl.handle.net/20.500.12684/4567
dc.identifier.volume30en_US
dc.identifier.wosWOS:000383914600002en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherLippincott Williams & Wilkinsen_US
dc.relation.ispartofAlzheimer Disease & Associated Disordersen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAlzheimer diseaseen_US
dc.subjectmiRNAs biogenesis pathway genetic variationen_US
dc.subjectSNP biomarkersen_US
dc.subjectupstream candidate genesen_US
dc.subjectperipheral molecular diagnosticsen_US
dc.titleSNP Variation in MicroRNA Biogenesis Pathway Genes as a New Innovation Strategy for Alzheimer Disease Diagnostics: A Study of 10 Candidate Genes in an Understudied Population From the Eastern Mediterraneanen_US
dc.typeArticleen_US

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