engleski

The role of 5HT-related genes in autism: association study

Objectives: 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 represent one of the biological substrates of this disorder. Alterations in the expression of one or more 5HT-related genes might lead to the dysregulation of 5HT transmission in the brain, affecting so its early development and resulting in autistic behavioral symptoms. We have studied the association of the following 5HT-related genes: tryptophan hydroxylase 1 and 2 (Tph1, Tph2), monoamine oxidase A and B (MAOA, MAOB), 5HT transporter (5HTT) and 5HT2A receptor (5HT2Ar) with autism in the Croatian population. Materials and Methods: DNA was isolated from blood samples of 103 autistic and 368 control subjects and genotyped, using polymerase chain reaction and restriction analysis, for A218C Tph1, G703T Tph2, uVNTR MAOA, A/G MAOB, 5HTT-LPR and -1438AG 5HT2Ar polymorphisms. Distributions of alleles and genotypes were compared between the autistic and control groups. Results: There were no significant differences in the distribution of alleles and genotypes of the Tph, MAO and 5HTT polymorphisms between autistic and control subjects. However, a significant difference in the distribution of genotypes (p = 0.014) adn alleles (p = 0.0054) of the 5HT2Ar polymorphism has been observed, with an increased incidence of G allele and GG genotype in the autistic group. In addition, an increase in the relative autistic to control subject ratio followed the increase in number of G alleles. The observed trend was significant (p = 0.0035). Conclusion: The results provide evidence for the association of the 5HT2Ar gene with autism in the Croatian population and indicate a possible role of this 5HT-related gene in susceptibility to autism spectrum disorders.

autism; tryptophan hydroxylase; monoamine oxydase; serotonin transporter; 5HT2A receptor; gene polymorphisms

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