Possible interaction of alcohol dehydrogenase and aldehyde dehydrogenase genes with the dopamine D2 receptor gene in anxiety-depressive alcohol dependence.
BACKGROUND
The role of the dopamine D2 receptor (DRD2) gene in the development of alcohol abuse or dependence is controversial. The controversy is due in part to the disparate definitions pertaining to the control groups used and to the definitions of subtypes in alcohol dependence. In the Han Chinese population, the alcohol dehydrogenase 1B*2/*2 (ADH1B*2/*2) genotype and the aldehyde dehydrogenase 2*2 (ALDH2*2) allele have been considered as protective factors against alcohol abuse or dependence. Moreover, the ADH1B and ALDH2 genes might be involved in dopamine metabolism. We hypothesized that the ADH1B and ALDH2 genes might interact with the DRD2 gene and that the association between the DRD2 gene and alcohol dependence might be affected by different ADH1B and ALDH2 genotypes. This study examined whether the DRD2 gene is associated with specific subtypes of alcohol dependence and evaluated the relationship between the DRD2 gene and alcohol-metabolizing genes in a specific subtype of alcohol dependence.


METHODS
Of the 465 Han Chinese subjects who were recruited for the study, 71 were classified with pure alcohol dependence, 113 with both alcohol dependence and anxiety-depression (ANX/DEP ALC), and 129 with anxiety-depression but without alcohol dependence (ANX/DEP). The remaining 152 subjects were supernormal controls. All subjects were interviewed with the Chinese version of the modified Schedule of Affective Disorders and Schizophrenia-Lifetime; all alcohol dependence, anxiety, and major depressive diagnoses were made according to DSM-IV criteria.


RESULTS
The DRD2 gene was not found to be associated with pure alcohol dependence or ANX/DEP, but was found to be associated with ANX/DEP ALC. Furthermore, the association between the DRD2 gene and ANX/DEP ALC was shown to be under the control of the ALDH2*1/*1 and ADH1B*1/*2 genotypes.


CONCLUSIONS
ANX/DEP ALC is a specific subtype of alcohol dependence. Because ANX/DEP ALC was associated with the DRD2 gene only under the stratification of ADH1B*1/*2 or ALDH2*1/*1, the DRD2 gene might interact with the ADH1B gene and the ALDH2 gene, respectively, in the development of ANX/DEP ALC in the Taiwan Han Chinese population.
Huang
San-Yuan
SY
Department of Psychiatry, Tri-Service General Hospital, Graduate Institute of Medical Sciences, Taipei, Taiwan, Republic of China.
Lin
Wei-Wen
WW
Ko
Huei-Chen
HC
Lee
Jia-Fu
JF
Wang
Tso-Jen
TJ
Chou
Yuan-Hwa
YH
Yin
Shih-Jiun
SJ
Lu
Ru-Band
RB
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D001007:Anxiety / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D003863:Depression / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D017448:Receptors, Dopamine D2 / Q000235:genetics*
D017448:Receptors, Dopamine D2; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase