Genetički markeri oksidativnog stresa kod bolesnika sa manifestnim dijabetesom tipa 2 i aterosklerozom
Genetic markers of oxidative stress in patients with manifested diabetes type 2 and atherosclerosis
Author
Grubiša, Ivana I.Mentor
Milašin, Jelena
Committee members
Stamenković-Radak, Marina
Vučinić, Nada
Novaković, Ivana

Metadata
Show full item recordAbstract
Ateroskleroza je kompleksno i multifaktorsko oboljenje koje obuhvata veliki
broj tipova ćelija kao i brojne fiziološke procese. Veruje se da oksidativni stres igra
važnu ulogu u inicijaciji i progresiji ateroskleroze. Kardiovaskularne bolesti (CVD)
predstavljaju vodeći uzrok smrtnosti u Srbiji i pronalaženje markera oksidativnog stresa,
uključujući i genske varijante, doprinelo bi smanjenju broja obolelih.
Studija asocijacije, koja je obuhvatala 140 obolelih od diabetes mellitus tip 2 sa
kardiovaskularnim komplikacijama (DM+A), 60 obolelih od neke od kliničkih
manifestacija ateroskleroze (A) i 100 zdravih kontrola (K) je sprovedena da bi se
utvrdila značajnost polimorfizama gena koji su povezani sa oksidativnim stresom,
metabolizmom lipida i detoksifikacijom kao markera oksidativnog stresa i faktora rizika
za nastanak oboljenja. Za studiju su odabrani polimorfizmi gena čiji produkti imaju
antioksidativnu ulogu u plazmi (pon1 Q192R, L55M i C(-107)T), antioksidativnu ulogu
i ulogu u meta...bolizmu lipida u plazmi i ćeliji (apoE 112/158 polimorfizam) i
antioksidativnu i detoksifikujuću ulogu u ćeliji (GSTM1*0, GSTT1*0 i GSTP1
Ile105Val). Genomska DNK je izolovana ili iz ćelija periferne krvi ili iz epitelnih ćelija
bukalne sluzokože. Genotipizacija je rañena restrikcionom digestijom PCR produkata i
analizom dužine restrikcionih fragmenata (PCR-RFLP) na agaroznom ili
poliakrilamidnom gelu i real-time PCR metodom. Hi-kvadrat i Fišerov egzaktni test su
upotrebljeni za utvrñivanje razlika u distribuciji učestalosti ispitivanih genotipova i alela, a logističkom regresionom analizom utvrñivan je rizik za oboljevanje.
Atherosclerosis is a complex and multifactorial disorder that involves many cell
types and organs as well as many physiological processes. It is believed that the
oxidative stress plays a critical role in the initiation and progression of atherosclerosis.
Cardiovascular diseases (CVD) are the leading cause of death in Serbia and discovering
oxidative stress markers, including gene variants, would contribute to reducing the
number of patients.
A association study, comprised 140 patients with diabetes mellitus type 2 and
cardiovascular complications (DM+A), 60 patients with clinical manifestations of
atherosclerosis (A) and 100 healthy individuals (K), has been undertaken in order to
estimate the relevance of polymorphisms in genes related to oxidative stress, lipid
metabolism, and detoxification as oxidative stress markers and disease risk factors.
Polymorphisms in genes whose products exert an antioxidative role in the plasma (pon1
Q192R, L55M i C(-107)T), in both plasma and cells (apo...E 112/158 polymorphisms)
and antioxidative and detoxication role in cells (GSTM1*0, GSTT1*0 i GSTP1
Ile105Val) have been selected for the study. Genomic DNA was isolated from peripheral blood cells or from buccal epithelial cells. The genotyping was performed
using restriction digestion of PCR products and by analysis of restriction fragment
length (PCR-RFLP) on agarose or polyacrilamide gel electrophoresis and the real-time
PCR method.Chi-square and Fisher exact test were used for determination of
differences in the analyzed genotype and allele distribution frequencies, and logistic
regression analysis was used for disease risk assessment.