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Srpski arhiv za celokupno lekarstvo
2018, vol. 146, br. 11-12, str. 646-652
jezik rada: engleski
vrsta rada: originalan članak
objavljeno: 18/01/2019
doi: 10.2298/SARH180801069B
Broj kopija gena SMN1 kao modifikator preživljavanja kod bolesnika iz Srbije sa sporadičnom formom amiotrofične lateralne skleroze
aUniverzitet u Beogradu, Biološki fakultet
bUniverzitet u Beogradu, Medicinski fakultet + Klinički centar Srbije, Klinika za neurologiju, Beograd
cUniverzitet u Beogradu, Institut za biološka istraživanja 'Siniša Stanković'

e-adresa: milosb@bio.bg.ac.rs

Projekat

Analiza promena u strukturi genoma kao dijagnostički i prognostički parametar humanih bolesti (MPNTR - 173016)

Sažetak

Uvod/Cilj Amiotrofična lateralna skleroza (ALS) predstavlja teško oboljenje motornog neurona. Većina slučajeva je naizgled sporadična, sa varijantama u visokorizičnim ALS genima ili genima asociranim sa ALS. Dva gena asocirana sa ALS su SMN1, čije funkcionalno odsustvo uzrokuje spinalnu mišićnu atrofiju (SMA), i njemu gotovo identičan gen SMN2, koji je modifikator fenotipa SMA. Oba gena smeštena su u segmentalnoj duplikaciji 5q13.2. Cilj studije bio je ispitivanje asocijacije broja kopija gena SMN1 i SMN2, kao i gena SERF1 i NAIP, smeštenih u istom genomskom regionu, sa rizikom za razvoj bolesti i preživljavanje kod bolesnika iz Srbije sa sporadičnom formom ALS (SALS). Metode Multipla ligaciono-zavisna amplifikacija je korišćena za određivanje broja kopija gena SMN1, SMN2, SERF1 i NAIP u klinički detaljno okarakterisanoj grupi od 153 bolesnika sa SALS iz Srbije i 153 kontrolne osobe. Rezultati Asocijacija broja kopija gena SMN1, SMN2, SERF1 ili NAIP sa rizikom za razvoj SALS ili preživljavanjem nije pokazana. Krive preživljavanja zasnovane na multivarijabilnoj Koksovoj regresionoj analizi pokazale su da tri kopije SMN1, niži zbir skale ALSFRS-R u trenutku dijagnoze, brži pad zbira ALSFRS-R tokom vremena i kraće dijagnostičko kašnjenje rezultuju kraćim preživljavanjem bolesnika sa SALS iz Srbije. Zaključak Prognoza preživljavanja bolesnika sa SALS zasnovana na kliničkim parametrima može biti unapređena korišćenjem genetičkog parametra - broja kopija SMN1.

Ključne reči

preživljavanje motornog neurona; amiotrofična lateralna skleroza; H4F5; NAIP; SMN1

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