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

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Item Type:	Article
Title:	Association of attentional network function with exon 5 variations of the CHRNA4 gene
Creators Name:	Winterer, G., Musso, F., Konrad, A., Vucurevic, G., Stoeter, P., Sander, T. and Gallinat, J.
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.
Keywords:	Attention, Attention Deficit Disorder with Hyperactivity, Biological Models, European Continental Ancestry Group, Exons, Magnetic Resonance Imaging, Nicotine, Nicotinic Receptors, Parietal Lobe, Tobacco Use Disorder, Animals, Mice, Xenopus
Source:	Human Molecular Genetics
ISSN:	0964-6906
Publisher:	Oxford University Press
Volume:	16
Number:	18
Page Range:	2165-2174
Date:	15 September 2007
Official Publication:	https://doi.org/10.1093/hmg/ddm168
PubMed:	View item in PubMed

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