20.500.12556/DKUM-84122 Izbrani polimorfizmi genov oksidativnega stresa in pojavnost srčnega infarkta ter stopnja prizadetosti koronarnega žilja pri bolnikih s sladkorno boleznijo tipa 2 Selected polymorphisms of oxidative stress genes, prevalence of myocardial infarction, and the degree of coronary artery disease in patients with type 2 diabetes Kronični koronarni sindrom in miokardni infarkt (MI) sta pri sladkornih bolnikih tipa 2 (SBT2) posledica kronične hiperglikemije in zvišanih nivojev oksidativnega stresa. V svoji retrospektivni asociacijski študiji smo raziskovali vpliv polimorfizmov genov, ki vplivajo na nivo oksidativnega stresa v telesu in na druge patofiziološke poti v procesu ateroskleroze. Od 1471 preiskovancev s SBT2 jih je 378 doživelo MI (primeri). Preiskovali smo povezave s polimorfizmi rs6060566 gena ROMO1, rs1333049 gena CDKN2B-AS1, rs841 gena GCH1, rs1800566 gena NQO1, rs702483 gena RAC1, rs9349379 gena PHACTR1 in rs3739998 gena JCAD. Dokazali smo povezavo MI s polimorfizmoma rs1333049 in rs3739998. Vsem preiskovancem smo izmerili nivo 8-hidroksi-2′-deoksigvanozina (8-OHdG) za določitev stopnje oksidativnega stresa, vendar razlik med primeri in kontrolami nismo našli. Tudi v povezavi s preiskovanimi polimorfizmi razlik v nivoju 8-OHdG ni bilo. 146 bolnikov s SBT2 je opravilo koronarno računalniško tomografsko angiografijo (CCTA). Našli smo povezavo med alelom C polimorfizma rs6060566 gena ROMO1 in ≥ 50 % – ≤75 % zožitvami koronarnih arterij. Polimorfizme rs6060566, rs1333049, rs1800566, rs9349379, rs3739998 smo opredelili kot polimorfizme tveganja. MI je bil pogosteje prisoten pri posameznikih z večjim številom prisotnih genotipov tveganja in s prisotnostjo ≥ 4 alelov tveganja. Z večjim številom alelov tveganja je bila višja ocena kalcinacij koronarnih arterij (CAC). V endarteriektomijskem tkivu koronarnih arterij 40 bolnikov smo dokazali večjo ekspresijo ROMO1 pri nosilcih alela C rs6060566. Chronic hyperglycemia and elevated oxidative stress levels in patients with type 2 diabetes (T2DM) ultimately result in chronic coronary syndrome and myocardial infarction (MI). In our retrospective association study, we explored the impact of gene polymorphisms that affect oxidative stress levels or are involved in other pathophysiological atherosclerotic pathways. Of the 1471 investigated subjects with T2DM, 378 have experienced MI (controls). We investigated links between MI and polymorphisms rs6060566 of ROMO1 gene, rs1333049 of CDKN2B-AS1 gene, rs841 of GCH1 gene, rs1800566 of NQO1 gene, rs702483 of RAC1 gene, rs9349379 of PHACTR1 gene and rs3739998 of JCAD gene. We have demonstrated an association of MI with rs1333049 and rs3739998. We measured levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) in all participants to determine the degree of oxidative stress, though we did not find any differences between cases and controls. In addition, there were no differences in the 8-OHdG levels regardless of investigated polymorphism. Coronary computed tomography angiography (CCTA) was performed on 146 diabetic patients. C Allele of the rs6060566 ROMO1 was associated with coronary artery stenosis of ≥50%-≤75%. Polymorphisms rs6060566, rs1333049, rs1800566, rs9349379, and rs3739998 were defined as risk polymorphisms. We demonstrated a greater risk of MI with more risk genotypes and ≥4 risk alleles. Likewise, the coronary artery calcium score was higher with more risk alleles. In endarteriectomy tissues of the coronary arteries of 40 patients, we have shown higher expression of ROMO1 in rs6060566 C allele carriers. miokardni infarkt sladkorna bolezen tipa 2 oksidativni stres koronarna bolezen polimorfizem myocardial infarction type 2 diabetes mellitus oxidative stress coronary artery disease polymorphism true true false [M. Tibaut] Slovenski jezik Angleški jezik Doktorska disertacija 2023-04-15 10:34:27 2024-06-17 11:26:02 2024-06-18 03:23:08 0000-00-00 00:00:00 2024 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.127-005.8:612.015(043.3) 197708803 DOK_Tibaut_Miha_2024.pdf DOK_Tibaut_Miha_2024.pdf 1 3DCFB9BB7394F65CC9DC7B6EEC57B6E9 cc4a8e0c48e01dab948f8348db02eaf2083c020bc5f8dfcd5d6fb2cf576058ee 21218f8f-140e-11ef-88d0-00155d000105 https://dk.um.si/Dokument.php?lang=slv&id=179376 Medicinska fakulteta 0 0 0