engleski

The role of serotonin transporter SLC6A4 in behavioral disorders

Serotonin (5-hydroxytryptamine, 5HT) is a biologically active molecule with many physiological functions in mammals, including regulation of brain development and neurotransmission. Alterations in brain 5HT homeostasis have been indicated as biological substrates in several behavioural and psychiatric disorders. The 5HT transporter (5HTt) mediates the reuptake of serotonin into the presynaptic neuron, thus regulating the magnitude and duration of 5HT synaptic action. The 5HTt gene contains two functional polymorphisms: 5-HTTLPR, a 22 bp-VNTR in the promoter (16-repeat "long" (L) allele is more efficient in transcription than the 14-repeat "short" (S) variant), and VNTR-2, a 17 bp-VNTR in the second intron repeated 9, 10 or 12 times (the 12-repeat allele has stronger enhancer-like properties). In order to examine the possible roles of the 5HTt gene in the predisposition to alcoholism, schizophrenia, suicidal behaviour, and autism, we performed case-control or family-based association studies. The lack of association of 5HTt gene polymorphisms with autism suggests that either 5HTt is not involved in development of autism or that the 5HTt action mechanism does not involve the examined polymorphisms. On the other hand, the preferential transmission of the 5-HTTLPR allele S in families with alcoholic probands, the preferential transmission of the VNTR-2 allele 12 in families with schizophrenic probands, and the significant excess of haplotype L10 among suicide victims in comparison to healthy controls, point to an association of the 5HTt gene with these three disorders, indicate a possible involvement of 5HTt in respective serotonergic imbalances, and suggest focusing on 5HTt in the use of 5HT-directed therapy.

5HTt; 5-HTTLPR; VNTR-2; case-control study; preferential transmission

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