Genetic Variation Underpinning ADHD Risk in a Caribbean Community.
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ABSTRACT:
SUBMITTER: Puentes-Rozo PJ
PROVIDER: S-EPMC6721689 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Publications
Genetic Variation Underpinning ADHD Risk in a Caribbean Community.
Puentes-Rozo Pedro J PJ Acosta-López Johan E JE Cervantes-Henríquez Martha L ML Martínez-Banfi Martha L ML Mejia-Segura Elsy E Sánchez-Rojas Manuel M Anaya-Romero Marco E ME Acosta-Hoyos Antonio A García-Llinás Guisselle A GA Mastronardi Claudio A CA Pineda David A DA Castellanos F Xavier FX Arcos-Burgos Mauricio M Vélez Jorge I JI
Cells 20190816 8
Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and prevalent neurodevelopmental disorder that frequently persists into adulthood. Strong evidence from genetic studies indicates that single nucleotide polymorphisms (SNPs) harboured in the <i>ADGRL3</i> (<i>LPHN3</i>), <i>SNAP25</i>, <i>FGF1</i>, <i>DRD4</i>, and <i>SLC6A2</i> genes are associated with ADHD. We genotyped 26 SNPs harboured in genes previously reported to be associated with ADHD and evaluated their potential a ...[more]
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Project description:ADHD is the most common neurobehavioral disorder in school-aged children. In addition to genetic factors, environmental influences or gene x environmental interactions also play an important role in ADHD. One example of a well studied environmental risk factor for ADHD is exposure to polychlorinated biphenyls (PCBs). In this study, we investigated whether the well-established genetic model of ADHD based on the Spontaneously Hypertensive Rat (SHR) and a well established PCB-based model of ADHD exhibited similar molecular changes in brain circuits involved in ADHD. The brains from 28 male rats (8 SHR, 8 Sprague-Dawley (SD) controls, 8 Wistar-Kyoto (WKY) controls, and 4 PCB-exposed SD rats) were harvested at postnatal day 55-65 and RNA was isolated from six brain regions of interest. The RNA was analyzed for differences in expression of a set of 308 probe sets interrogating 218 unique genes considered highly relevant to ADHD or epigenetic gene regulation using the Rat RAE 230 2.0 GeneChip (Affymetrix). Selected observations were confirmed by real time quantitative RT-PCR. The results show that the expression levels of genes Gnal, COMT, Adrbk1, Ntrk2, Hk1, Syt11 and Csnk1a1 were altered in both the SHR rats and the PCB-exposed SD rats. Arrb2, Stx12, Aqp6, Syt1, Ddc and Pgk1 expression levels were changed only in the PCB-exposed SD rats. Genes with altered expression only in the SHRs included Oprm1, Calcyon, Calmodulin, Lhx1 and Hes6.The epigenetic genes Crebbp, Mecp2 and Hdac5 are significantly altered in both models. The data provide strong evidence that genes and environment can affect different set of genes in two different models of ADHD and yet result in the similar disease-like symptoms. The brains from 28 male rats (8 SHR, 8 Sprague-Dawley (SD) controls, 8 Wistar-Kyoto (WKY) controls, and 4 PCB-exposed SD rats) were harvested at postnatal day 55-65 and RNA was isolated from six brain regions of interest. The RNA was analyzed for differences in expression of a set of 308 probe sets interrogating 218 unique genes considered highly relevant to ADHD or epigenetic gene regulation using the Rat RAE 230 2.0 GeneChip (Affymetrix). Selected observations were confirmed by real time quantitative RT-PCR.
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2011-04-15 | E-BUGS-108 | biostudies-arrayexpress
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