Stand der Ursachen - Mitteldeutsche Psychiatrietage 2011

Poster | Sucht
P31
Family history of alcoholism: Specific genetic influence of NR2A variants on early
onset of drinking and alcohol dependence
C. Altmann, Halle/Saale
Introduction: There is evidence to support the hypothesis that a positive family history (FHP) of alcohol
dependence (AD) in first-degree relatives is a significant risk factor for an individual to develop AD in his
lifetime. However, little is known about the role of specific candidate genes variants which may transmit
this risk. The aim of this CIGAR (Collaborative initiative on Genetics of alcoholism in Central Europe)
analyses is to investigate the influence of known candidate gene variants (ADH4, GABRA2, NR2A) posing a
risk for AD on age of first drinking and age of onset in FHP vs. FHN (family history negative) individuals.
Methods: 1843 inpatient subjects diagnosed with AD according to DSM-IV criteria from three addiction
treatment centres were included. Characteristics of AD and related phenotypes ages at first drinking (FD)
and alcohol dependence onset (ADO) were obtained using standardized structured interviews. All subjects
were genotyped for ADH4 (rs1800759) , GABRA2 (rs9291283) and NR2A (rs2072450) polymorphisms which
were all reported from previous studies in this multi-center sample to be associated with alcohol
dependence (Preuss et al 2010; Soyka et al 2008; Schumann et al 2008).
Results: FHP vs. FHN individuals had significant more severe characteristics of alcohol dependence and
more comorbidity. FD before age 15 was associated with higher rates of ADO before 30 in FHP. Variants of
NR2A and ADH4 were associated with early FD, daily alcohol intake and ADO in male FHP individuals while
ADH4 rs1800759 was associated with FHP vs FHN.
Discussion: This study results confirm the significant role of FHP in development of alcohol dependence.
The results also support the relationship of ADH4 and NR2A variants with FHP and related traits in the
development of AD and suggest that these patients carry a significant genetic risk which is influenced by
specific variants of candidate genes.
8. Mitteldeutsche Psychiatrietage | 95