Association of attentional network function with exon 5 variations of the CHRNA4 gene.

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Winterer G, Musso F, Konrad A, Vucurevic G, Stoeter P, Sander T, Gallinat J

Association of attentional network function with exon 5 variations of the CHRNA4 gene.

Hum Mol Genet. 2007 Sep 15;16(18):2165-74. Epub 2007 Jul 5.

PubMed ID

17613539 [ View in PubMed

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Abstract

Mutational analyses in xenopus oocyte and mice models indicate that the positive effect of nicotine on attention may be modulated by genetic variations within exon 5 of the alpha4 subunit of the nicotinergic acetylcholine receptor gene CHRNA4. The potential relevance of exon 5 is further emphasized by two recent family-based association studies of nicotine dependence because subgroups of nicotine-dependent subjects are thought to 'self-medicate' attentional deficits with nicotine. We investigated a synonymous single nucleotide polymorphisms (SNP): rs1044396, which has recently been associated with nicotine-dependence, plus two adjacent synonymous SNPs rs1044394 and rs1044393 in exon 5 of n = 47 unrelated healthy Caucasian subjects (age: 22.7 +/- 1.7 years; sex: n = 23 males; regular smokers: n = 19). Attentional network function was assessed in supplementary motor area/anterior cingulate (SMA/ACC) and parietal cortex with functional magnetic resonance imaging during an attention-requiring visual oddball task. SNP rs1044396 showed genotype effects on attentional network function both in the SMA/ACC and parietal cortex in the absence of overt behavioral effects. In the parietal cortex, a gene-dosage effect was seen. Comparable genotype effects were also found for the other two SNPs. This investigation provides first evidence that attentional network function may be modulated by genetic variations within CHRNA4 exon 5. If confirmed, future studies need to address what 'functional' polymorphisms are causative for the observed effects.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Nicotine	Neuronal acetylcholine receptor subunit alpha-4	Protein	Humans	Yes	Agonist	Details