Lack of Association Between Down Syndrome and Polymorphisms in Dopamine Receptor D4 and Serotonin Transporter Genes

Abstract

Down Syndrome (DS) patients suffer from cognitive dysfunction, depression, hyperactivity, irritability etc. Dopamine (DA) and serotonin (5HT) are known to control cognitive and behavioral attributes. An increased number of the DA receptor 4 (DRD4) is detected in brain regions primarily involved in cognition. Impairments in executive function have also been reported with depletion in 5HT. A variable number of tandem repeat (VNTR) in the exon 3 of DRD4 and an insertion/deletion polymorphism in the promoter region of 5HT transporter (5HTTLPR) have been found to be associated with different neurobehavioral disorders; however, association of these polymorphisms with DS has never been explored. The present family-based analysis on DS revealed significant over-transmission of a DRD4 VNTR allele which encodes for D4 receptor with average activity. No association was noticed for the 5HTTLPR. We may conclude that these genetic polymorphisms are not contributing to the neuromotor and cognitive dysfunctions observed in DS.

VNTR-DAT1 and COMTVal158Met Genotypes Modulate Mental Flexibility and Adaptive Behavior Skills in Down Syndrome

“…We here did not explore these variants and thus, possible interactions of our polymorphisms and the DRD4 gene variants could also be contributing to the detected phenotypes. Other genotypes examined seem to little contribute (genetic polymorphisms in the dopaminergic and serotonergic system the DRD4 exon 3 VNTR and the 5-HTTLPR) to the cognitive dysfunctions observed in DS ( Das Bhowmik et al, 2008 ).…”

“…However, only two studies have explored DA genetic polymorphisms. A family-based analysis revealed significant over-transmission of a DRD4 VNTR allele, which encodes for D4 dopamine receptor for DS ( Das Bhowmik et al, 2008 ). In a second study, the 7-repeat allele of the DRD4 polymorphism was associated to behavioral and executive functions difficulties in children with DS ( Mason et al, 2015 ).…”

Interference-Free Determination of Dopamine at the Poly(thionine)-Modified Glassy Carbon Electrode

“…8 5-HT-containing neurons modulate behavioral and psychological processes, for example mood, sleep and emotions, as well as depression, anxiety, alcoholism and drug dependency. 9 Due to the very low concentration of DA in biological systems and it coexistence with AA, UA and 5-HT, a highly sensitive and selective analytical method is in high demand for the detection of DA.…”