Abstract
The dopamine transporter (DAT1) is a membrane spanning protein that binds the neurotransmitter dopamine and performs re-uptake of dopamine from the synapse into a neuron. The gene encoding DAT1 consists of 15 exons spanning 60 kb on chromosome 5p15.32. Several studies have investigated the possible associations between variants in DAT1 gene and psychiatric disorders. The present study aimed to determine the distribution of the variable number of tandem repeat (VNTR) polymorphism in the 3′ untranslated region of DAT1 in 12 Indian populations. A total of 471 healthy unrelated individuals in 12 Indian populations from 3 linguistic groups were included in the present study. The analysis was carried out using PCR and electrophoresis. Overall, 4 alleles of the DAT1 40-bp VNTR, ranging from 7 to 11 repeats were detected. Heterozygosity indices were low and varied from 0.114 to 0.406. The results demonstrate the variability of the DAT1 40-bp VNTR polymorphism in Indian populations and revealed a high similarity with East Asian populations.
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References
Giros B, Caron M (1993) Molecular characterization of the dopamine transporter. Trends Pharmacol Sci 14:43–49
Vandenbergh DJ, Persico AM, Hawkins AL et al (1992) Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. Genomics 14:1104–1106
Ueno S, Nakamura M, Mikami M (1999) Identification of a novel polymorphism of the dopamine transporter (DAT1) gene and significant association with alcoholism. Mol Psychiatry 4:552–557
Martinez D, Gelernter J, Abi-Dargham A (2001) The variable number of tandem repeats polymorphism of the dopamine transporter gene is not associated with significant change in dopamine transporter phenotype in humans. Neuropsychopharmacology 24:553–560
Kirley A, Lowe N, Hawi Z et al (2003) Association of the 480 bp DAT1 allele with methylphenidate response in a sample of Irish children with ADHD. Am J Med Genet B Neuropsychiatr Genet 121:50–54
Gainetdinov RR, Fumagalli F, Jones SR et al (1997) Dopamine transporter is required for in vivo MPTP neurotoxicity: evidence from mice lacking the transporter. J Neurochem 69:1322–1325
Bois P, Jeffreys AJ (1999) Minisatellite instability and germline mutation. Cell Mol Life Sci 55:1636–1648
Vandenbergh DJ, Thompson MD, Cook EH et al (2000) Human dopamine transporter gene: coding region conservation among normal, Tourette’s disorder, alcohol dependence and attention-deficit hyperactivity disorder populations. Mol Psychiatry 5:283–292
Persico AM, Vandenbergh DJ, Smith SS et al (1993) Dopamine transporter gene polymorphisms are not associated with polysubstance abuse. Biol Psychiatry 34:265–267
Persico AM, Bird G, Gabbay FN et al (1996) D2 dopamine receptor gene TaqI A1 and B1 restriction fragment length polymorphisms: enhanced frequencies in psychostimulant-preferring polysubstance abusers. Biol Psychiatry 40:776–784
Bamshad M, Kivisild T, Watkins WS et al (2001) Genetic evidence on the origins of Indian caste populations. Genome Res 11:994–1004
Thanseem I, Thangaraj K, Chaubey G et al (2006) Genetic affinities among the lower castes and tribal groups of India: inference from Y chromosome and mitochondrial DNA. BMC Genet 7:42
Thangaraj K, Joshi MB, Reddy AG et al (2002) CAG repeat expansion in the androgen receptor gene is not associated with male infertility in Indian populations. J Androl 23:815–818
Goudet J (1995) FSTAT (version 1.2): a computer program to calculate F-statistics. J Hered 86:485–486
Jacobsen LK, Staley JK, Zoghbi SS et al (2000) Prediction of dopamine transporter binding availability by genotype: a preliminary report. Am J Psychiatry 157:1700–1703
Miller GM, Madras BK (2001) Polymorphisms in the 3′-untranslated region of human and monkey dopamine transporter genes affect reporter gene expression. Molecular Psychiatry 7:44–55
Fuke S, Suo S, Takahashi N et al (2001) The VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expression. Pharmacogenomics J 1:152–156
Kang AM, Palmatier MA, Kidd KK (1999) Global variation of a 40-bp VNTR in the 3′-untranslated region of the dopamine transporter gene (SLC6A3). Biol Psychiatry 46:151–160
Galeyeva AR, Iur’ev EB, Khusnutdinova EK (2001) Polymorphism of the dopamine transporter gene in populations of the Volga-Ural region. Genetika 37:1018–1020
Sano A, Kondoh K, Kakimoto Y et al (1993) A 40-nucleotide repeat polymorphism in the human dopamine transporter gene. Hum Genet 91:405–406
Gelernter J, Kranzler H, Lacobelle J (1998) Population studies of polymorphisms at loci of neuropsychiatric interest (tryptophan hydroxylase (TPH), dopamine transporter protein (SLC6A3), D3 dopamine receptor (DRD3), apolipoprotein E (APOE), mu opioid receptor (OPRM1), and ciliary neurotrophic factor (CNTF)). Genomics 52:289–297
Banoei MM, Chaleshtori MH, Sanati MH et al (2007) Diversity and relationship between Iranian ethnic groups: human dopamine transporter gene (DAT1) VNTR genotyping. Am J Hum Biol 19:821–826
Mitchell RJ, Howlett S, Earl L et al (2000) Distribution of the 3′ VNTR polymorphism in the human dopamine transporter gene in world populations. Hum Biol 72:295–304
Sander T, Harms H, Podschus J et al (1997) Allelic association of a dopamine transporter gene polymorphism in alcohol dependence with withdrawal seizures or delirium. Biol Psychiatry 41:299–304
Schmidt LG, Harms H, Kuhn S et al (1998) Modification of alcohol withdrawal by the A9 allele of the dopamine transporter gene. Am J Psychiatry 155:474–478
Sander T, Berlin W, Ostapowicz A et al (2000) Variation of the genes encoding the human glutamate EAAT2, serotonin and dopamine transporters and susceptibility to idiopathic generalized epilepsy. Epilepsy Res 41:75–81
Franke P, Schwab SG, Knapp M et al (1999) DAT1 gene polymorphism in alcoholism: a family-based association study. Biol Psychiatry 45:652–654
Heinz A, Goldman D, Jones DW et al (2000) Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 22:133–139
Muramatsu T, Higuchi S (1995) Dopamine transporter gene polymorphism and alcoholism. Biochem Biophys Res Commun 211:28–32
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This research work was supported by a grant from Department of Biotechnology, Government of India (project no. BT/PR3607/SPD/09/261/2003).
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Bhaskar, L.V.K.S., Thangaraj, K., Mulligan, C.J. et al. Dopamine transporter (DAT1) VNTR polymorphism in 12 Indian populations. Neurol Sci 30, 487–493 (2009). https://doi.org/10.1007/s10072-009-0139-2
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DOI: https://doi.org/10.1007/s10072-009-0139-2