Genetika i epigenetika u poremećajima iz spektra autizma

Abstract

Uvod: Poremećaji iz spektra autizma predstavljaju klinički i etiološki veoma heterogenu grupu. Etiopatogeneza ovih, u osnovi, neurorazvojnih poremećaja je više od dve decenije predmet istraživanja velikog broja istraživača, a uključuje složene genetske, sredinske i epigenetske mehanizme. Cilj: Cilj rada je bio da se sagleda udeo genetskih i epigenetskih faktora u nastanku poremećaja iz spektra autizma. Metod: Pregled dostupne i relevantne literature. Rezultati: Pokazalo se da genetski faktor značajno povećava rizik za razvoj poremećaja iz spektra autizma, u preko 50% slučajeva. Identifikovano je više od 100 gena koji se dovode u vezu sa ovim poremećajima. Pored genetskih varijanti koje su relativno česte, prisutna je tendencija prijavljivanja retkih de novo mutacija. Epigenetski mehanizmi, metilacija DNK i hemijska modifikacija histona su mehanizmi koji utiču na ekspresiju gena ne menjajući primarnu strukturu gena. Na promene u metilaciji DNK mogu da utiču određene genske mutacije, ali i faktori sredine - posebno oni koji vode oksidativnom stresu, što menja regulaciju genske ekspresije. Tako je kod nekih osoba sa autizmom uočena hipermetilacija delova DNK koji se nalaze u okolini regiona koji su od značaja za neurorazvoj. Zaključak: Dosadašnja genetska istraživanja su omogućila sagledavanje poremećaja iz spektra autizma iz jednog novog ugla i razumevanje njihove etiopatogeneze kao složene interakcije različitih gena i faktora sredine, kao predispoziciju za nastanak ovih poremećaja.

Introduction: Autism spectrum disorders are clinically and etiologically a very heterogeneous group. The etiopathogenesis of these, basically, neurodevelopmental disorders has been the subject of research by a large number of researchers for more than two decades, and includes complex genetic, environmental and epigenetic mechanisms. Aim: The aim of this paper was to review the role of genetic and epigenetic factors in the development of autism spectrum disorders. Method: Review of available and relevant literature. Results: Genetic factor has been shown to significantly increase the risk of developing autism spectrum disorders, in over 50% of cases. More than 100 genes have been identified that are linked to these disorders. In addition to genetic variants that are relatively common, there is a tendency to report rare de novo mutations. Epigenetic mechanisms, DNA methylation and chemical modification of histones, are mechanisms that affect gene expression without altering the primary structure of the gene. Changes in DNA methylation can be influenced by certain gene mutations, but also by environmental factors - especially those that lead to oxidative stress, which changes the regulation of gene expression. Thus, in some people with autism, hypermethylation of DNA parts found in the vicinity of the region that are important for neurodevelopment has been observed. Conclusion: Previous genetic research has made it possible to view autism spectrum disorders from a new angle and to understand their etiopathogenesis as a complex interaction of different genes and environmental factors, as a predisposition for the development of these disorders.