Association of a Met88Val diazepam binding inhibitor (DBI) gene polymorphism and anxiety disorders with panic attacks

Thoeringer, Christoph K.; Binder, Elisabeth B.; Salyakina, Daria; Erhardt, Angelika; Ising, Marcus; Unschuld, Paul G.; Kern, N.; Lucae, Susanne; Brueckl, T.; Mueller, Marianne; Fuchs, B.; Puetz, Benno; Lieb, Roselind; Uhr, Manfred; Holsboer, Florian; Mueller-Myhsok, Bertram; Keck, Martin E.

doi:10.1016/j.jpsychires.2006.06.001

Cited by 31 publications

(10 citation statements)

References 33 publications

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“…The 5 UTR AVPR1A SNP rs3759292, indicated in this study, is located 179 bp 5 to the microsatellite polymorphisms rs9325177 and rs11283312 that were linked to autism, personality traits and altruism (Knafo et al 2008;Meyer-Lindenberg et al 2008;Wassink et al 2004). DBI SNP rs2289948, indicated in this study, is in complete LD with SNP rs8192506 that was associated with alcoholism in Japanese (Waga et al 2007) and with anxiety disorders with panic attacks in EA (Thoeringer et al 2007). The second DBI SNP rs12613135, indicated in this study, is located in the same haplotype block with SNPs rs2289948 and rs8192506.…”

Section: Discussionmentioning

confidence: 56%

Heroin addiction in African Americans: a hypothesis‐driven association study

Levran¹,

Londoño

O’Hara³

et al. 2009

Genes Brain and Behavior

103

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Heroin addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify gene variants associated with heroin addiction in African Americans. The emphasis was on genes involved in reward modulation, behavioral control, cognitive function, signal transduction and stress response. We have performed a case-control association analysis by screening with 1350 variants of 130 genes. The sample consisted of 202 former severe heroin addicts in methadone treatment and 167 healthy controls with no history of drug abuse. Single nucleotide polymorphism (SNP), haplotype and multi-SNP genotype pattern analyses were performed. Seventeen SNPs showed point-wise significant association with heroin addiction (nominal P < 0.01). These SNPs are from genes encoding several receptors: adrenergic (ADRA1A), arginine vasopressin (AVPR1A), cholinergic (CHRM2), dopamine (DRD1), GABA-A (GABRB3), glutamate (GRIN2A) and serotonin (HTR3A) as well as alcohol dehydrogenase (ADH7), glutamic acid decarboxylase (GAD1 and GAD2), the nucleoside transporter (SLC29A1) and diazepambinding inhibitor (DBI). The most significant result of the analyses was obtained for the GRIN2A haplotype G-A-T (rs4587976-rs1071502-rs1366076) with protective effect (P uncorrected = 9.6E-05, P corrected = 0.058). This study corroborates several reported associations with alcohol and drug addiction as well as other related disorders and extends the list of variants that may affect the development of heroin addiction. Further studies will be necessary to replicate these associations and to elucidate the roles of these variants in drug addiction vulnerability.

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Section: Discussionmentioning

confidence: 56%

Heroin addiction in African Americans: a hypothesis‐driven association study

Levran¹,

Londoño

O’Hara³

et al. 2009

Genes Brain and Behavior

103

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“…Besides the GABRA subunit genes, several other GABAergic systems have been implicated in the genetic load of GABA system pathways on the psychobiology of anxiety. Suggestive signals for an association with anxiety disorders and anxiety-related personality traits have been found for other genes, e.g., glutamic acid decarboxylase 1 (Hettema et al, 2006) and 2 (Smoller et al, 2001b), b3 subunits of the GABAA receptor (Feusner et al, 2001), the diazepam binding inhibitor (Thoeringer et al, 2007), and the GABA transporter 1 (Thoeringer et al, 2009). The latter authors suggest a multiple system hit-theory in the genetic basis of anxiety disorders; many loci at different genes of the GABA system, each with a small effect, contribute to an individual’s risk on anxiety disorder.…”

Section: Preclinical Genetic Approaches To Anxietymentioning

confidence: 99%

The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders

2013

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There is ample evidence that genetic factors play an important role in anxiety disorders. In support, human genome-wide association studies have implicated several novel candidate genes. However, illumination of such genetic factors involved in anxiety disorders has not resulted in novel drugs over the past decades. A complicating factor is the heterogeneous classification of anxiety disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) and diverging operationalization of anxiety used in preclinical and clinical studies. Currently, there is an increasing focus on the gene × environment (G × E) interaction in anxiety as genes do not operate in isolation and environmental factors have been found to significantly contribute to the development of anxiety disorders in at-risk individuals. Nevertheless, extensive research on G × E mechanisms in anxiety has not resulted in major breakthroughs in drug discovery. Modification of individual genes in rodent models has enabled the specific study of anxiety in preclinical studies. In this context, two extensively studied neurotransmitters involved in anxiety are the gamma-aminobutyric acid (GABA) and 5-HT (5-hydroxytryptamine) system. In this review, we illustrate the complex interplay between genes and environment in anxiety processes by reviewing preclinical and clinical studies on the serotonin transporter (5-HTT), 5-HT1A receptor, 5-HT2 receptor, and GABAA receptor. Even though targets from the serotonin and GABA system have yielded drugs with known anxiolytic efficacy, the relation between the genetic background of these targets and anxiety symptoms and development of anxiety disorders is largely unknown. The aim of this review is to show the vast complexity of genetic and environmental factors in anxiety disorders. In light of the difficulty with which common genetic variants are identified in anxiety disorders, animal models with translational validity may aid in elucidating the neurobiological background of these genes and their possible role in anxiety. We argue that, in addition to human genetic studies, translational models are essential to map anxiety-related genes and to enhance our understanding of anxiety disorders in order to develop potentially novel treatment strategies.

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“…The 5′ UTR AVPR1A SNP rs3759292 is in close proximity to the two microsatellite polymorphisms (rs9325177 and rs11283312) that were found to be associated with autism and personality (Knafo et al, 2008; Wassink et al, 2004; Meyer-Lindenberg et al, 2009). The DBI SNP rs2289948 is in complete LD with SNP rs8192506 that was found to be associated with alcoholism in Asians (Waga et al, 2007) and with anxiety in EA (Thoeringer et al, 2007). The DBI SNP rs12613135 is located in the same haplotype block with SNPs rs2289948 and rs8192506.…”

Section: Association Studiesmentioning

confidence: 99%

Common and specific liability to addiction: Approaches to association studies of opioid addiction

Nielsen

Kreek

2012

Drug and Alcohol Dependence

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Background Opioid addiction, whether to opiates such as heroin and morphine, and/or to non-medical use of opioids, is a major problem worldwide. Although drug-induced and environmental factors are essential for the vulnerability to develop opioid addiction, the genetic background of an individual is now known also to play a substantial role. Methods The overall goal of this article is to address the common and specific liabilities to addiction in the context of approaches to studies of one addiction, opioid addiction. Literature on identifying genetic variants that may play a role in the development of opioid addiction was reviewed. Results A substantial number of genetic variants have been reported to be associated with opioid addiction. No single variant has been found in any of the reported GWAS studies with a substantial effect size on the vulnerability to develop heroin addiction. It appears that there is a complex interaction of a large number of variants, some rare, some common, which interact with the environment and in response to specific drugs of abuse to increase the vulnerability of developing opioid addiction. Conclusions In spite of the inherent difficulties in obtaining large well-phenotyped cohorts for genetic studies, new findings have been reported that are being used to develop testable hypotheses into the biological basis of opioid addiction.

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Association of a Met88Val diazepam binding inhibitor (DBI) gene polymorphism and anxiety disorders with panic attacks

Cited by 31 publications

References 33 publications

Heroin addiction in African Americans: a hypothesis‐driven association study

Heroin addiction in African Americans: a hypothesis‐driven association study

The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders

Common and specific liability to addiction: Approaches to association studies of opioid addiction

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