D2 dopamine receptor gene haplotypes and their influence on alcohol and tobacco consumption magnitude in alcohol-dependent individuals. 2007

U W Preuss, and P Zill, and G Koller, and B Bondy, and M Sokya
Pediatric Hospital of Ludwig-Maximilians-University, Munich, Germany. ulrich.preuss@medizin.uni-halle.de

BACKGROUND Alcohol dependence and habitual smoking frequently co-occur and possibly mutually influence each other. Both have been related to alterations of dopaminergic neurotransmission. The aim of this analysis of the Munich Gene Data Bank for Alcoholism(MGBA) was to re-evaluate the potential relation between D2 receptor and dopamine transporter gene haplotypes and quantity-related phenotypes of alcohol consumption (average daily alcohol intake before admission for treatment) and smoking (average units smoked per day). METHODS A total of 333 inpatients (265 males) were enrolled in the study, all of who met the ICD10 diagnosis of alcohol dependence. Mild and strong quantity drinkers and smokers were separated into groups by median split. A number of genetic markers were chosen across D2 dopamine receptor gene (-141 Ins/Del, Taq1B, Taq1D, Ser311Cys; rs1079594 (intron 7); Taq1A) and dopamine transporter (40bp variable number of tandem repeat; rs2617605 (intron 2); rs37022 (intron 7); rs40184 (intron 14)). Genotyping was performed using PCR. RESULTS Strong drinkers reported significantly higher amounts of smoking and vice versa. While no association was detected for dopamine transporter genetic variants, a number of D2 receptor gene single nucleotide polymorphisms were related to both smoking- and drinking-related behaviours. Subsequent analysis of D2 receptor gene haplotypes revealed that two common haplotypes had a significant association with quantitative phenotypes of regular drinking (Ins-C-G-C-A1) and smoking (Ins-T-G-A-A2). CONCLUSIONS The finding of an association between common D2 dopamine receptor gene haplotypes with the quantity of drinking and smoking corroborates with results from previous studies suggesting a relationship between the dopamine system and alcohol and substance use disorders. Furthermore, it makes D2 dopamine receptor a candidate gene significantly influencing both alcohol and nicotine dependence.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D005260 Female Females
D005787 Gene Frequency The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION. Allele Frequency,Genetic Equilibrium,Equilibrium, Genetic,Allele Frequencies,Frequencies, Allele,Frequencies, Gene,Frequency, Allele,Frequency, Gene,Gene Frequencies
D006239 Haplotypes The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX. Haplotype
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000428 Alcohol Drinking Behaviors associated with the ingesting of ALCOHOLIC BEVERAGES, including social drinking. Alcohol Consumption,Alcohol Intake,Drinking, Alcohol,Alcohol Drinking Habits,Alcohol Drinking Habit,Alcohol Intakes,Consumption, Alcohol,Drinking Habit, Alcohol,Habit, Alcohol Drinking,Habits, Alcohol Drinking,Intake, Alcohol
D012907 Smoking Willful or deliberate act of inhaling and exhaling SMOKE from burning substances or agents held by hand. Smoking Behaviors,Smoking Habit,Behavior, Smoking,Behaviors, Smoking,Habit, Smoking,Habits, Smoking,Smoking Behavior,Smoking Habits
D017448 Receptors, Dopamine D2 A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES. Dopamine D2 Receptors,Dopamine-D2 Receptor,D2 Receptors, Dopamine,Dopamine D2 Receptor,Receptor, Dopamine-D2

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