Differential Genetic Effect of the Norepinephrine Transporter Promoter Polymorphisms on Attention Problems in Clinical and Non-clinical Samples

Z. Nemoda, Nora Angyal, Zsanett Tarnok, Emma Birkas, Emese Bognar, M. Sasvári, J. Gervai, K. Lakatos

Research output: Contribution to journalArticle

Abstract

Among the monoaminergic modulatory neurotransmitters, norepinephrine is involved in task orienting, hence noradrenergic genetic variants have been studied in connection to attentional processes. The role of this catecholamine system is also highlighted by the selective norepinephrine transporter blocking atomoxetine, which has proved to be effective in the pharmacological treatment of Attention Deficit Hyperactivity Disorder (ADHD). In the present genetic association study three single nucleotide polymorphisms (rs28386840, rs2242446, rs3785143 SNPs) were analyzed from the 5′ region of the norepinephrine transporter (NET, SLC6A2) gene, which have been linked to ADHD previously. Attention problems scores of the mother-rated Child Behavior Checklist (CBCL) were used in separate analyses of 88 preschoolers (59.1% male, 6 years of age) recruited from the general population and 120 child psychiatry patients with ADHD diagnosis (85.8% male, age: 9.8 ± 2.9). The NET SNPs showed associations with attention problems, but the direction was different in the two groups. Regarding the promoter variant rs28386840, which showed the most consistent association, the T-allele-carrier patients with ADHD had lower CBCL attention problems scores compared to patients with AA genotype (p = 0.023), whereas T-allele-carriers in the community sample had more attention problems (p = 0.042). Based on previous reports of lower NE levels in ADHD children and the inverted-U shape effect of NE on cognitive functions, we propose that rs28386840 (- 3081) T-allele, which is associated with lower NET expression (and potentially higher synaptic NE level) would support attention processes among ADHD patients (similarly as atomoxetine increases NE levels), whereas it would hinder cortical functions in healthy children.

Original languageEnglish
Article number1051
JournalFrontiers in Neuroscience
Volume13
Issue numberJAN
DOIs
Publication statusPublished - Jan 1 2019

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Norepinephrine Plasma Membrane Transport Proteins
Attention Deficit Disorder with Hyperactivity
Single Nucleotide Polymorphism
Alleles
Child Behavior
Checklist
Child Psychiatry
Genetic Association Studies
Cognition
Catecholamines
Neurotransmitter Agents
Norepinephrine
Genotype
Mothers
Pharmacology
Population
Genes

Keywords

  • ADHD (attention deficit hyperactivity disorder)
  • Catecholamine
  • Inattention
  • Member 2)
  • Noradrenaline
  • SLC6A2 (solute carrier family 6

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Differential Genetic Effect of the Norepinephrine Transporter Promoter Polymorphisms on Attention Problems in Clinical and Non-clinical Samples. / Nemoda, Z.; Angyal, Nora; Tarnok, Zsanett; Birkas, Emma; Bognar, Emese; Sasvári, M.; Gervai, J.; Lakatos, K.

In: Frontiers in Neuroscience, Vol. 13, No. JAN, 1051, 01.01.2019.

Research output: Contribution to journalArticle

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