Dopamine transporter (DAT1) VNTR polymorphism and alcoholism in two culturally different populations of south India.
It is well established that the central dopaminergic reward pathway is likely involved in alcohol intake and the progression of alcohol dependence. Dopamine transporter (DAT1) mediates the active re-uptake of DA from the synapse and is a principal regulator of dopaminergic neurotransmission. The gene for the human DAT1 displays several polymorphisms, including a 40-bp variable number of tandem repeats (VNTR) ranging from 3 to 16 copies in the 3'-untranslated region (UTR) of the gene. To assess the role of this gene in alcoholism, we genotyped the VNTR of DAT1 gene in a sample of 206 subjects from the Kota population (111 alcohol dependence cases and 95 controls) and 142 subjects from Badaga population (81 alcohol dependence cases and 61 controls). Both populations inhabit a similar environmental zone, but have different ethnic histories. Phenotype was defined based on the DSM-IV criteria. Genotyping was performed using PCR and electrophoresis. The association of DAT1 with alcoholism was tested by using the Clump v1.9 program which uses the Monte Carlo method. In both Kota and Badaga populations, the allele A10 was the most frequent allele followed by allele A9. The genotypic distribution is in Hardy-Weinberg equilibrium in both cases and control groups of Kota and Badaga populations. The DAT1 VNTR was significantly associated with alcoholism in Badaga population but not in Kota population. Our results suggest that the A9 allele of the DAT gene is involved in vulnerability to alcoholism, but that these associations are population specific.
Centre for Cellular and Molecular Biology, Hyderabad, India.
Lakkakula V K S
LV
Bhaskar
Kumarasamy
K
Thangaraj
Samiksha
S
Wasnik
Lalji
L
Singh
Vadlamudi
V
Raghavendra Rao
D020413:3' Untranslated Regions; D000437:Alcoholism / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005838:Genotype; D006801:Humans; D007194:India; D018598:Minisatellite Repeats / Q000235:genetics*; D011110:Polymorphism, Genetic
D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human