Povezanost polimorfizama gena za glutation S-transferaze i izloženosti prenatalnim faktorima okoline kod osoba sa poremećajima autističnog spektra

Abstract

Uvod: poremećaji spektra autizma (PSA) su grupa kompleksnih psihijatrijskih poremećaja, za koje je pretpostavljeno da nastaju kao posledica interakcije gena i okoline. Jedan od mehanizama koji bi mogao da objasni i genetsku i komponentu okoline u okviru ove grupe poremećaja je oksidativni stres. Cilj ovog istraživanja je da se ispita potencijalna uloga čestih polimorfizama gena za glutation transferaze A1, M1, T1 i P1 u razvoju poremećaja spektra autizma. Pored toga, ispitivana je interakcija gena i okoline specifična za oksidativni stres u povećanju rizika za razvoj PSA, i to u odnosu na česte pre- i perinatalne faktore rizika i GST polimorfizme. Metodologija: ova studija slučajeva i kontrola uključivala je 113 pacijenata sa poremećajem spektra autizma koji su lečeni hospitalno ili ambulantno u okviru Klinike za decu i omladinu Instituta za mentalno zdravlje, u periodu od oktobra 2009. do decembra 2011., i 114 kontrola koje su uparene po polu i uzrastu. Kontrolnu grupu činili su deca, adolescenti i mlađi odrasli koji se leče na Odeljenju za urologiju, kao i Odeljenju za ortopediju Univerzitetske dečije klinike u Beogradu, u periodu od oktobra 2011. do juna 2012. godine. Dijagnoza PSA je postavljena na osnovu ICD-10 kriterijuma, i potvrđena na osnovu Revidiranog dijagnostičkog intervjua za autizam (Autism Diagnostic Interview – Revised (ADI-R)). Vekslerova skraćena skala inteligencije (Wechsler Abbreviated Scale of Intelligence - WASI) korišćena je za određivanje intelektualnog funkcionisanja kod verbalnih pacijenata, dok je Vineland skala adaptivnog ponašanja (Vineland Adaptive Behavior Scales, Second Edition - Vineland-II) korišćena kod neverbalnih pacijenata. U grupi pacijenata i kontrola primenjen je upitnik izloženosti faktorima rizika tokom trudnoće. Takođe, u obe grupe utvrđeni su genotipovi GSTA1, GSTM1, GSTP1 i GSTT1, i ispitan je njihov individualni i zajednički efekat...

Background: autism spectrum disorders (ASD) are a group of complex psychiatric disorders, with supposed gene environment interaction in their etiology. One of the mechanisms that could explain both the genetic and environmental component is oxidative stress. The aim of this research was to explore the potential role of common GSTA1, M1, T1 and P1 gene polymorphisms in ASD. In addition to that, we have explored the oxidative stress specific gene environment interaction, regarding common pre- and perinatal risk factors and GST polymorphisms. Methods: this case control study included 113 cases diagnosed with ASD, treated at the Clinic for children and adolescents at the Institute of Mental health, during the period from October 2009 to December 2011, and 114 age and sex matched controls. The control group consisted of children, adolescents and young adults treated at the Department of urology and Orthopedics at the University Childrens Clinic in Belgrade, during the period from October 2011 to June 2012. The diagnosis of ASD was made based on ICD-10 Criteria, and confirmed based on Autism Diagnostic Interview – Revised (ADI-R). The Wechsler Abbreviated Scale of Intelligence - (WASI) was used to assess the intellectual functioning in verbal cases, while the Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) was used in nonverbal cases. The questionnaire regarding exposure to risk factors during pregnancy was administered in both groups. Also, we explored the GSTA1, GSTM1, GSTP1 i GSTT1 genotypes, as well as their individual and combined effect. Results: exploring the sex-specific characteristics of the case group showed that boys were significantly more often diagnosed with typical autism (F84.0). There were no sex differences in the severity of symptoms (ADI-R), neither in adaptive functioning (Vineland II). A sex-specific development of symptoms with age was confirmed. Also, the results showed that there are sexspecific profiles of prediction of adaptive functioning by clinical symptoms...