Udruženost polimorfizma gena renin-angiotenzin sistema u razvoju dijabetesne nefropatije kod bolesnika sa dijabetesom tipa 1
Sažetak
Uvod/Cilj. Dijabetesna nefropatija (DN) kao jedna od najznačajnijih komplikacija dijabetesa melitusa (DM) uključuje progresivno povećanje urinarne ekskrecije albumina koja udružena sa hipertenzijom, dovodi do terminalne bubrežne insuficijencije. Hipertenzija i povećana aktivnost renin-angiotenzin sistema (RAS) uz prisustvo određenih polimorfizama gena za RAS, angiotenzinogen (AGT), angiotenzin-konvertujući enzim (ACE) i angiotenzinski receptor tipa 1 (AT1R) mogu da ukažu na povećanu sklonost ka razvoju DN. Cilj rada bio je ispitivanje distribucije polimorfizma gena AGT, ACE i AT1R u grupi bolesnika sa DM tipa 1 u odnosu na stepen razvoja nefropatije, definisane kliničke parametre i faktore rizika. Metode. Ispitivanjem je bilo obuhvaćeno 79 bolesnika sa DM tipa 1, starosti 20–40 godina, trajanjem dijabetesa duže od 5 godina i bez drugih hroničnih bolesti. Polimorfizam gena RAS ustanovljen je metodom PCR-RFLP korišćenjem restrikcione endonukleaze Psy I (Tth 111I) i Hae III. Rezultati. Bolesnici sa proteinurijom u odnosu na normo- i mikroalbuminurične ispitanike značajno su se razlikovali po godinama starosti, trajanju dijabetesa, vrednosti krvnog pritiska, hipertenzije, retinopatije i urinarne ekskrecije albumina (p < 0,001). U ispitivanim grupama, razlike u učestalosti genskih polimorfizama za ACE i AT1R nisu bile statistički značajne. Prisustvo TT genotipa u M235T polimorfizmu gena za AGT bio je značajno viši u grupi bolesnika sa proteinurijom (p < 0,05). Učestalost nefropatije bila je 5,2 puta veća (OR = 5,20, p < 0,05) kod dijabetičara sa hipertenzijom, dok je TT genotip ukazivao na 28.38 puta veću sklonost (OR = 28,389, p < 0,01) ka razvoju nefropatije u odnosu na MM genotip. Zaključak. Povećanje učestalosti hipertenzije i TT alelske forme u angiotenzinogen genskom polimorfizmu kod bolesnika u terminalnom stadijumu nefropatije mogu imati značaj za određivanje markera procene rizika od nastanka komplikacija u dijabetesu melitusu tipa 1.
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