Genetic Variation in the Atrial Natriuretic Peptide Transcription Factor GATA4 Modulates Amygdala Responsiveness in Alcohol Dependence

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• 作者：Anne Jorde^a ; ^{anne.jorde@zi-mannheim.de" class="auth_mail} ; Patrick Bach^a ; Stephanie H. Witt^b ; Kathleen Becker^a ; Iris Reinhard^c ; Sabine Vollstä ; dt-Klein^a ; Martina Kirsch^a ; Derik Hermann^a ; Katrin Charlet^f ; Anne Beck^f ; Lioba Wimmer^g ; Josef Frank^b ; Jens Treutlein^b ; Rainer Spanagel^d ; Karl Mann^a ; Henrik Walter^e ; Andreas Heinz^f ; Marcella Rietschel^b ; Falk Kiefer^a
• 关键词：Alcohol dependence ; ANP ; cue-reactivity ; fMRI ; GATA4 ; imaging genetics
• 刊名：Biological Psychiatry
• 出版年：15 May 2014
• 年：2014
• 卷：75
• 期：10
• 页码：790-797
• 全文大小：639 K

文摘

Two genome-wide association studies recently showed alcohol dependence to be associated with a single-nucleotide polymorphism (rs13273672) located on a gene (GATA4) that encodes a transcription factor of atrial natriuretic peptide (ANP). A growing body of evidence suggests that ANP might be involved in the symptomology of alcohol dependence. This study examined whether reactivity to alcohol cues in the ANP target region amygdala, a key area implicated in addictive behavior, differs depending on the GATA4 genotype of a patient. We also investigated potential associations between these differences in amygdala activation and relapse behavior.

Methods

Eighty-one abstinent, alcohol-dependent patients completed a functional magnetic resonance imaging cue-reactivity task in a 3-Tesla scanner and provided blood samples for DNA extraction.

Results

The results showed significantly lower alcohol-cue-induced activations in G-allele carriers as compared with AA-homozygotes in the bilateral amygdala. A survival analysis revealed that a stronger alcohol-specific amygdala response predicted a lowered risk for relapse to heavy drinking in the AA-homozygotes, whereas this effect could not be observed in G-allele carriers.

Conclusions

These results illuminate potential underlying mechanisms of the involvement of the GATA4 gene in the etiology of alcohol dependence via its influence on ANP and amygdala processing.