POVEZANOST PTPN22 I DIJABETES MELITUS TIP 1
Ključne reči:
Dijabetes melitus tip 1, PTPN22, polimorfizam, decaApstrakt
Dijabetes melitus je multifaktorijalno metaboličko obolenje čija etiologija pokazuje značajnu genetsku osnovu. Dijabetes melitus tipa 1 (T1DM) je najčešća hronična dečja bolest. Ova autoimuna endokrina bolest pogađa mlađe ljude i najviše se manifestuje u pubertetu. Karakteriše je degeneracija β ćelija endokrinog pankreasa, što dovodi do nedostatka insulina. Polimorfizmi gena uključenih u patogenezu dijabetesa tipa 1 i drugih autoimunih bolesti privlače sve veću pažnju istraživača poslednjih godina. Među njima, više studija je utvrdilo povezanost polimorfizma u genu koji kodira protein tirozin fosfatazu-22 (PTPN22) sa T1DM. PTPN22 eksprimiraju mnoge ćelije imunskog sistema, kao što su T i B limfociti, monociti, dendritične ćelije i NK ćelije. PTPN22 gen kodira limfoid tirozin fosfatazu (LYP), koja je inhibitor aktivacije T ćelija. rs2476601 (R620W, 1858C→T) je jedna od najviše proučavanih varijacija LYP. Ova mutacija rezultuje delimičnim ili potpunim prekidom vezivanja PTPN22 za CSK (C-terminalna Src kinaza). C1858T polimorfizam unutar ovog gena doprinosi razvoju T1DM jer smanjuje aktivaciju T limfocita. Mnoge studije predlažu ovaj polimorfizam kao značajan faktor rizika za pojavu T1DM kod belaca. Međutim, ova oblast istraživanja pokazuje veliki potencijal za razvoj preventivnih tretmana za T1DM, pa čak i veliku šansu za primenu u skrining testovima, dok pacijenti sa T1DM varijantom PTPN22 predstavljaju ciljnu grupu za ispitivanje prevencije sa visoko selektivnim inhibitorima LYP.
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