TY - JOUR
T1 - Identification and functional characterisation of a novel dopamine beta hydroxylase gene variant associated with ADHD
AU - Tong, Janette
AU - McKinley, Leigh-Anne
AU - Cummins, Tarrant
AU - Johnson, Beth
AU - Matthews, Natasha
AU - Vance, Alasdair
AU - Heussler, Helen
AU - Gill, Michael
AU - Kent, Lindsey
AU - Belgrove, Mark
AU - Hawi, Ziarih
PY - 2015
Y1 - 2015
N2 - Dysregulation in neurotransmitter signalling has been implicated in the aetiology of ADHD. Polymorphisms of the gene encoding dopamine beta hydroxylase (DBH), a key player in catecholamine signalling, have been shown to be associated with increased risk for ADHD. Previous genetic studies of ADHD have reported associations with a range of DBH gene variants (rs2519152, rs1611115, rs1108580 and rs6271) however small sample sizes have led to inconsistency. Here we conducted TDT analysis in a large ADHD sample of 794 nuclear families to re-examine the relationship between DBH and ADHD.
Although we did not replicate associations of rs2519152 and rs1611115 with ADHD, we identified a significant association with rs129882 (pcorrected = 0.02). Further, gene reporter assays of DBH rs129882 showed a significant impact of the ADHD-associated C allele on luciferase expression in a human neuroblastoma cell line, SH-SY5Y. These data demonstrate for the first time that a DBH gene variant which confers risk to ADHD is also associated with reduced in vitro gene expression.
AB - Dysregulation in neurotransmitter signalling has been implicated in the aetiology of ADHD. Polymorphisms of the gene encoding dopamine beta hydroxylase (DBH), a key player in catecholamine signalling, have been shown to be associated with increased risk for ADHD. Previous genetic studies of ADHD have reported associations with a range of DBH gene variants (rs2519152, rs1611115, rs1108580 and rs6271) however small sample sizes have led to inconsistency. Here we conducted TDT analysis in a large ADHD sample of 794 nuclear families to re-examine the relationship between DBH and ADHD.
Although we did not replicate associations of rs2519152 and rs1611115 with ADHD, we identified a significant association with rs129882 (pcorrected = 0.02). Further, gene reporter assays of DBH rs129882 showed a significant impact of the ADHD-associated C allele on luciferase expression in a human neuroblastoma cell line, SH-SY5Y. These data demonstrate for the first time that a DBH gene variant which confers risk to ADHD is also associated with reduced in vitro gene expression.
KW - Attention Deficit Disorder with Hyperactivity
KW - Genetics
KW - Gene expression
KW - DBH
KW - Polymorphism
UR - http://informahealthcare.com/doi/abs/10.3109/15622975.2015.1036771
U2 - 10.3109/15622975.2015.103677
DO - 10.3109/15622975.2015.103677
M3 - Article
SN - 1562-2975
JO - World Journal of Biological Psychiatry
JF - World Journal of Biological Psychiatry
ER -