engleski

The role of serotonin system in autism: relationship between polymorphic gene variants and platelet serotonin level

Autism is a neurodevelopmental syndrome, with onset in early childhood, characterized by social and communication dysfunction and stereotypic behaviors. Recent findings indicate that disturbances in serotonergic (5HT) neurotransmission might represent one of the biological substrates of this disorder. Increased 5HT levels in blood, constistently found in ~30% of autistic patients, might be the consequence of increased peripheral 5HT synthesis or platelet 5HT uptake, or of decreased platelet 5HT release or peripheral 5HT metabolism. Since the elements that control the peripheral 5HT levels (tryptophan hydroxylase - TPH, 5HT transporter - 5HTt, 5HT2A receptor - 5HT2Ar, and monoamine oxydase A - MAOA, respectively) are also present in the brain, alterations in their expression could lead to hyperserotonemia in the periphery, with simultaneous dysregulation of 5HT transmission in the brain. In this work we have studied the potential influence of allelic variants of the genes encoding the above mentioned 5HT elements, on the platelet 5HT levels in autistic patients. Platelet 5HT levels were determined in blood samples from 63 autistic individuals. DNA was isolated and genotyped for the following polymorphisms: a218c of TPH, 5HTTLPR of 5HTt, -1438AG of 5HT2Ar and u-VNTR of MAOA. While there were no significant influence of 5HTt and 5HT2Ar genotypes on the platelet 5HT level, significantly higher 5HT levels, of about 25%, were observed in individuals with cc genotype of TPH /p<0.02) and individuals with 4 repeats of MAOA (p<0.03), compared to the individuals with other genotypes of the respective polymorphisms. If we considered TPH-cc and MAOA-4 as "high 5HT" genotypes, a significant increase in the mean 5HT levels was observed with the increase in the number of "high 5HT" genotypes (p<0.009), pointing at the possible synergistic effect of the two genes. Although the functionality of the studied polymorphisms remains to be clarified, the obtained results indicate the involvement of TPH and MAOA genes in dysregulation of the peripheral 5HT homeostasis in autistic subjects and suggest their potential role in development of autistic disorder.

hyperserotonemia; gene polymorphism

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