HFE GENE MUTATION AND DOWN SYNDROME

Abstract

Sindrom Down (DS) predstavlja jedan od vodećih uzroka intelektualne zaostalosti te usporenog kognitivnog razvoja u humanoj populaciji. Do četrdesete godine, osobe s DS razvijaju neuropatlogiju i demenciju karakterističnu za Alzheimerovu bolest (AD). Brojna istraživanja povezala su metale, kao što je željezo, s patogenezom Alzheimerove bolesti. Jedan od mnogih proteina uključenih u održavanje homeostaze željeza u stanicama je protein za hemokromatozu (HFE). Promjene u ekspresiji HFE proteina su pronađene u mozgu oboljelih od AD. Istraživanja pokazuju da mutacije HFE gena, C282Y i H63D, doprinose neravnoteži željeza u organizmu. Cilj ovog istraživanja bio je ispitati je li mutacije C282Y i H63D HFE gena, zasebno ili u kombinaciji, predstavljaju rizični čimbenik za razvijanje rano nastupajuće AD u osoba s DS. Metode: Analiza HFE mutacija provedena je na uzorku od 180 osoba s DS i 200 zdravih kontrola pomoću PCR – RFLP metode. Statistička obrada podataka napravljena je koristeći 2 i Fisherov. Rezultati: Rezultati su pokazali da nema statistički značajnih razlika u distribuciji i učestalosti ispitivanih alela i genotipova kao ni njihovh kombinacija između grupe ispitanika s DS i kontrole grupe. Mutacije C282Y i H63D, HFE gena ne predstavljaju rizični čimbenik za prekomjerno nakupaljanje željeza a time i razvoj ranonastupajuće AD u osoba s DS.Down syndrome (DS) is caused by trisomy of chromosome 21, and is the one of major genetic causes of intellectual disability. By the age of 40 all DS individuals develop neuropatology and dementia seen in Alzheimer's disease (AD). Numerous studies have implicated metals such as iron in the pathogenesis of AD. One of many proteins involved in maintaining iron homeostasis is the hemochromatosis protein (HFE). Alterations in the expression pattern of HFE protein were found in brains of AD patients. Mutations of HFE gene, C282Y and H63D, were shown to affect body iron status. The aim of the study: C282Y and H63D mutations of HFE gene, individually or in combination, contribute to neurodegeneration and could be risk factors for early onset AD in DS individuals. Genotyping was done in 180 DS individuals and 200 healthy controls using PCR-RFLP methods. The frequencies of alleles and genotypes are compared between groups using the 2 and Fisher's exact tests. The results don’t show a statistically significant difference in distribution and frequency of alleles and genotypes between DS group and control group. We can conclude that H63D and C282Y mutation of HFE gene in our study group, were not associated with iron accumulation and early onset AD in DS individuals