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To achieve a better understanding of the pathways modulated by rs17070145 and its associated functional variant(s), we used laser capture microdissection (LCM) and RNA\u2010sequencing to investigate the effect of rs17070145 genotypes on whole transcriptome expression in the human hippocampus (HP) of 22 neuropathologically normal individuals, with a specific focus on the dentate gyrus (DG) and at the pyramidal cells (PC) of CA1 and CA3 sub\u2010regions. Differential expression analysis of RNA\u2010seq data within the HP based on the rs17070145 genotype revealed an overexpression of genes involved in the MAPK signaling pathway, potentially driven by the T\/T genotype. The most important contribution comes from genes dysregulated within the DG region. Other genes significantly dysregulated, and not involved in the MAPK pathway (Adj <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01 and Fold Change\u2009&gt;\u2009|1.00|) were: <jats:italic>RSPO4<\/jats:italic> (HP); <jats:italic>ARC<\/jats:italic>, <jats:italic>DUSP5<\/jats:italic>, <jats:italic>DNAJB5<\/jats:italic>, <jats:italic>EGR4<\/jats:italic>, <jats:italic>PPP1R15A<\/jats:italic>, <jats:italic>WBP11P1<\/jats:italic>, <jats:italic>EGR1<\/jats:italic>, <jats:italic>GADD45B<\/jats:italic> (DG); <jats:italic>CH25H<\/jats:italic>, <jats:italic>HSPA1A<\/jats:italic>, <jats:italic>HSPA1B<\/jats:italic>, <jats:italic>TNFSF9<\/jats:italic>, and <jats:italic>NPAS4<\/jats:italic> (PC). Several evidences suggested that the MAPK signaling pathway is linked with memory and learning processes. In non\u2010neuronal cells, the KIBRA protein is phosphorylated by ERK1\/2 (involved in the MAPK signaling) in cells as well as <jats:italic>in vitro<\/jats:italic>. Several of the other dysregulated genes are involved in memory and learning processes, as well as in Alzheimer's Disease. In conclusion, our results suggest that the effect of the <jats:italic>WWC1<\/jats:italic> rs17070145 polymorphism on memory performance and Alzheimer's disease might be due to a differential regulation of the MAPK signaling, a key pathway involved in memory and learning processes.<\/jats:p>","DOI":"10.1002\/hipo.22731","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T23:19:13Z","timestamp":1491434353000},"page":"784-793","source":"Crossref","is-referenced-by-count":26,"title":["Whole transcriptome profiling of the human hippocampus suggests an involvement of the KIBRA rs17070145 polymorphism in differential activation of the MAPK signaling pathway"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0139-098X","authenticated-orcid":false,"given":"Ignazio S","family":"Piras","sequence":"first","affiliation":[{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona 85004"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonida","family":"Krate","sequence":"additional","affiliation":[{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona 85004"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Schrauwen","sequence":"additional","affiliation":[{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona 85004"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason J","family":"Corneveaux","sequence":"additional","affiliation":[{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona 85004"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geidy E","family":"Serrano","sequence":"additional","affiliation":[{"name":"Civin Laboratory of Neuropathology at Banner Sun Health Research Institute Sun City Arizona 85351"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Sue","sequence":"additional","affiliation":[{"name":"Civin Laboratory of Neuropathology at Banner Sun Health Research Institute Sun City Arizona 85351"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G","family":"Beach","sequence":"additional","affiliation":[{"name":"Civin Laboratory of Neuropathology at Banner Sun Health Research Institute Sun City Arizona 85351"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Huentelman","sequence":"additional","affiliation":[{"name":"Neurogenomics Division Translational Genomics Research Institute Phoenix Arizona 85004"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12189"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_6_4_1","unstructured":"Bonferroni C. 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