A Common Haplotype of the Dopamine Transporter Gene Associated With Attention-Deficit/Hyperactivity Disorder and Interacting With Maternal Use of Alcohol During Pregnancy

Abstract

The identification of a common haplotype in 2 independent populations is an important step toward identifying functionally significant regions of DAT1. Interaction between DAT1 genotypes and maternal use of alcohol during pregnancy suggests that DAT1 moderates the environmental risk and has implications for the prevention of ADHD. Further studies are required to delineate the precise causal risk factor involved in this interaction.

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes

“…8 More recently investigation of genetic variation in DAT1 in English and Taiwanese samples suggested that the association is specific to a haplotype of the 10-repeat allele, with the 3-repeat allele of a second VNTR located within intron 8. 31 Analysis of these two markers in this sample revealed the same pattern, with only the 10-3 haplotype showing over transmission from heterozygote parents to their affected offspring (haplotype 34 and rs6347. 38,39 We detected a trend with over transmission of the same allele (A-allele) in rs6347 and no association with rs27072.…”

“…8,28 Standard PCR protocols were used for all VNTR markers and amplified products visualised on 2% agarose under UV light, as previously described. [31][32][33] SNP selection We adopted a 'biological systems' approach by nominating 46 genes that were likely to exert an effect through regulation of dopamine, serotonin and norepinephrine neurotransmission, as well as six circadian rhythm genes. Selected genes fell into the following functional groups: dopamine receptors, serotonin receptors, norepinephrine receptors, neurotransmitter metabolic and catabolic enzymes, neuronal transporters, synaptic vesicle associated proteins, fatty acid desaturase enzymes and circadian rhythm genes (listed in Table 1).…”

Replication of an association of a promoter polymorphism of the dopamine transporter gene and Attention Deficit Hyperactivity Disorder

“…One potential cause of heterogeneity could occur if only a subset of individuals carrying the 10-repeat allele is at risk for ADHD. This could arise if for example the DAT1 risk allele interacts with additional genetic or environmental risk factors, which vary in frequency between the different studies [6,18,20]. An alternative explanation, is that the 10-repeat allele is not the causative allele itself, but rather 'tags' a nearby functional variant that is only partially correlated with the 10-repeat allele.…”

“…An alternative explanation, is that the 10-repeat allele is not the causative allele itself, but rather 'tags' a nearby functional variant that is only partially correlated with the 10-repeat allele. Evidence for this comes from the observation in several studies that specific DAT1 haplotypes containing the 10-repeat allele confer risk for ADHD [3,4,6,13,16,17]. A c c e p t e d M a n u s c r i p t signal fell into two distinct groups of markers at the 3'and 5' ends of the gene.…”

Dopaminergic genotype biases spatial attention in healthy children

“…The 3 0 -UTR DAT1 polymorphism is a 40 bp VNTR with repeat copy numbers between 3 and 11, with the 10-repeat allele being the most frequent. The 10-repeat allele is thought to be a risk factor for ADHD 21,22 and has been associated with left-sided inattention in that disorder. 23,24 A number of in vitro studies suggest that the 10-repeat allele is associated with increased expression of DAT, relative to other alleles, such as the 9-repeat.…”