DRD2/ANKK1 TaqIA and SLC6A3 VNTR polymorphisms in alcohol dependence: association and gene-gene interaction study in a population of Central Italy.
Dopamine is a neurotransmitter whose functions are mediated by five receptors expressed in several organs and tissues. Dopaminergic system dysfunctions are involved in the etiology or treatment of several pathological conditions, including drug addiction. Alcohol dependence (AD) is a widespread psychiatric disorder, affecting 5.4% of the general population lifetime. Family and twins studies support the role of a genetic component in AD. Since dopamine neurotransmission has been shown to be involved in drug reward, related genes are plausible candidates for susceptibility to AD. Here, we evaluated both the DRD2/ANKK1 TaqIA (rs1800497) and SLC6A3 40 bp-VNTR SNP and gene-gene interaction analysis in AD patients from a population of Central Italy. The study design was a case-control. In total, 280 alcoholic subjects (213 men and 67 woman) and 280 age- and sex-matched control subjects were recruited for this study. Case subjects met the DSM-IV criteria for AD and they are free from any psychiatric co-morbidities. Controls were subjects who had non-alcohol problem either never drank; those who have smoked at least one pack of cigarettes per day for at least 1 year were excluded. Genotyping was performed by allele-specific PCR and RFLP-PCR. SLC6A3 40 bp 3'UTR-VNTR displays no association with AD. DRD2/ANKK1 TaqIA genotype distribution is significantly associated to AD (O.R.=1.551, p=0.023), with A1* allele displaying an O.R.=1.403 (p=0.029). Gene-gene interaction analysis using three-way contingency table analysis by a log-linear model yielded no significant result. Our study in a population of Central Italy extends and confirms previous results and, for the first time, tested the gene-gene interaction between SLC6A3 and DRD2 in AD.
School of Pharmacy, Experimental Medicine Unit, University of Camerino, Italy. fiorenzo.mignini@unicam.it
Fiorenzo
F
Mignini
Valerio
V
Napolioni
Claudia
C
Codazzo
Francesco M
FM
Carpi
Mario
M
Vitali
Marina
M
Romeo
Mauro
M
Ceccanti
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019973:Alcohol-Related Disorders / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics; D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D055815:Young Adult
D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases