ZNAČAJ INTERAKCIJA GENETSKIH I SREDINSKIH FAKTORA U ETIOLOGIJI MULTIPLE SKLEROZE
Sažetak
Multipla skleroza (MS) je imunološki posredovan poremećaj centralnog nervnog sistema. Najčešće se javlja kod mladih odraslih žena, a prevalencija raste sa geografskom širinom. Do sada je preko 200 gena, lokusa i jednonukleotidnih polimorfizama (SNP) povezano sa MS, iako svaki od njih samo neznatno doprinosi u sveukupnoj etiologiji bolesti. U studijama asocijacija na nivou genoma (GVAS) se pokazalo da haplotip HLA-DRB1*15:01 ima najjaču povezanost sa rizikom od pojave MS, a HLA-A*02 ima zaštitni efekat. Tačna etiologija MS je još uvek nejasna, ali izgleda da postoji interakcija između genetskog opterećenja pojedinca i faktora sredine koji doprinose nastanku MS kao što je infekcija Epstein-Barr virusom (EBV), nivo vitamina D, pušački status i gojaznost u ranom životnom dobu. Primećena je interakcija između HLA-DRB1*15:01 i EBV infekcije, najjačeg sredinskog faktora rizika za MS. Pretpostavlja se da je ova interakcija nastaje usleg toga što HLA-DRB1*15:01 deluje kao koreceptor za EBV, čime se pruža patofiziološko objašnjenje koje povezuje faktore sredine sa genetskim faktorima rizika za nastanak MS. Nedavno sprovedena studija koja je uključivala učesnike iz dve studije slučajeva i kontrola sa preko 13.000 uključenih ispitanika pokazala je da postoji interakcija između izlaganja suncu, nivoa vitamina D i HLA-DRB*15:01 statusa, sa povećanim rizikom od nastanka MS kod osoba sa nižom izloženošću sunčevim zracima, deficitom vitamina D i HLA-DRB*15:01 pozitivnim. Interakcija HLA-DRB1*15:01 sa pušenjem pronađena je u meta-analizi, dok je ista studija pokazala interakciju pušenja sa odsustvom HLA-A*02 samo u podskupu uključenih studija. Pokazalo se da rizik od MS varira kod gojaznih pojedinaca, pri čemu gojazne osobe sa podložnim genotipom (HLA-DRB1*15:01+, HLA-A*02-) imaju 16 puta veće šanse za MS u poređenju sa osobama koje nisu gojazne. sa genotipom koji nije podložan.
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