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Journal of Medical Biochemistry
2015, vol. 34, br. 4, str. 414-421
jezik rada: engleski
vrsta rada: izvorni naučni članak
objavljeno: 03/01/2020
PMC ID: PMC4922353
doi: 10.2478/jomb-2014-0060
Uticaj polimorfizama TNF-α (-308G/A) i IL-6 (-174G/C) gena na terapijski odgovor na etanercept u reumatoidnom artritisu
aUniverzitet u Beogradu, Farmaceutski fakultet, Institut za mikrobiologiju i imunologiju
bUniverzitet u Beogradu, Medicinski fakultet, Institut za reumatologiju
cUniverzitet u Beogradu, Institut za molekularnu genetiku i genetičko inženjerstvo

e-adresa: ijancic@pharmacy.bg.ac.rs

Projekat

Plastičnost imunskog sistema tokom starenja: imunomodulatorni potencijal estrogena (MPNTR - 175050)
Klinički značaj poremećaja urođene i stečene imunosti kod imunoinflamatornih i imunodeficitnih oboljenja (MPNTR - 175065)
Retke bolesti: molekularna patofiziologija, dijagnostički i terapijski modaliteti i socijalni, etički i pravni aspekti (MPNTR - 41004)

Sažetak

Uvod: Genetički faktori su značajni za predviđanje ishoda lečenja bolesnika sa reumatoidnim artritisom (RA). Cilj studije bio je da se ispita uticaj-308G/A TNF-α (rs 1800629) i -174G/C IL-6 (rs1800795) promotorskih polimorfizama na terapijski odgovor na etanercept. Metode: U studiju su bila uključena 73 pacijenta sa aktivnim RA. Terapijski odgovor je procenjivan posle 6 i 12 meseci terapije po kriterijumima Evropske lige protiv reumatizma. Genotipizacija pacijenata za polimorfizme -308G/A TNF-α i -174G/C IL-6 urađena je PCR-RFLP metodom i procenjivan je uticaj genotipova na odgovor na etanercept. Rezultati: Nije bilo razlike u procentu respondera (pacijenti kod kojih se DAS28 popravio > 1,2) između pacijenata sa TNF-α -308GG, GA i AA genotipom ni posle 6 ni posle 12 meseci tretmana. Posle 12 meseci lečenja procenat respondera je bio značajno veći kod pacijenata sa IL-6 -174GG u odnosu na pacijente sa GC ili CC genotipom (p= 0,006, x2 test). Poređenje pacijenata prema kombinovanim IL-6/TNF-α genotipovima pokazalo je da je IL-6 -174GG / TNF-α -308GG genotip učestaliji kod respondera u odnosu na druge kombinovane genotipove (p= 0.022, x2 test). Tačnije, svi pacijenti sa kombinovanim IL-6 -174GG / TNF-α -308GG genotipom bili su responderi posle 12 meseci terapije etanerceptom. Zaključak: Studija pokazuje da bolesnici sa genotipovima koji se povezuju sa manjom produkcijom TNF-α i IL-6 najbolje odgovaraju na terapiju etanerceptom.

Ključne reči

etanercept; reumatoidni artritis; farmakogenomika; 308G/A TNF-α genski polimorfizam; 174G/C IL-6 genski polimorfizam

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