Association of functional DBH genetic variants with alcohol dependence risk and related depression and suicide attempt phenotypes: results from a large multicenter association study.

Dopamine-beta-hydroxylase (DBH) metabolizes the conversion of dopamine to noradrenaline. DBH, located on chromosome 9q34.2 has variants with potential functional consequences which may be related to alterations of neurotransmitter function and several psychiatric phenotypes, including alcohol dependence (AD), depression (MD) and suicidal behavior (SA). The aim of this association study in a large multicenter sample of alcohol-dependent individuals and controls is to investigate the role of DBH SNPs and haplotypes in AD risk and associated phenotypes (AD with MD or SA). 1606 inpatient subjects with DSM-IV AD from four addiction treatment centers and 1866 control subjects were included. Characteristics of AD, MD and SA were obtained using standardized structured interviews. After subjects were genotyped for 4 DBH polymorphisms, single SNP case-control and haplotype analyses were conducted. rs1611115 (near 5') C-allele and related haplotypes were significantly associated with alcohol dependence in females. This association with female alcohol dependence also accounts for the significant relationship between this variant and comorbid conditions and traits. This study presents evidence for a potentially functional DBH variant influencing the risk for alcohol dependence while other comorbid conditions are not independently influenced by this SNP. However, the study also supports the possible role of the dopamine system in the etiology of female alcohol dependence.