Influence of casp8 -652 6n (rs3834129) polymorphism on oxidative stress biomarkers in patients with myocardial infarction

Abstract

Objective: This study aimed to evaluate the association between the CASP8 -652 6N insertion/deletion (rs3834129) polymorphism and oxidative stress biomarkers, malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and total antioxidant capacity (TAC), in Iraqi patients with MI.

Methods: A case-control study enrolled 60 MI patients and 30 age- and sex-matched healthy controls. Serum levels of MDA, 8-OHdG, and TAC were measured using enzyme-linked immunosorbent assay (ELISA). Genotyping of the CASP8 rs3834129 polymorphism was performed using amplification-refractory mutation system polymerase chain reaction (ARMS-PCR). Statistical analyses included independent t-tests, one-way ANOVA, Pearson correlation, and receiver operating characteristic (ROC) curve analysis.

Results: MI patients exhibited significantly higher MDA (23.9±6.8 vs. 10.4±3.9 nmol/ml, P<0.001) and TAC (0.072±0.001 vs. 0.034±0.002 mmol/l, P=0.025) concentrations compared to controls, while 8-OHdG showed a non-significant elevation (142.3±14.5 vs. 107.9±8.2 ng/ml, P=0.137). Age correlated positively with both 8-OHdG (r=0.625, P<0.001) and MDA (r=0.406, P=0.001). The CASP8 Ins/Ins genotype was more frequent among patients (90% vs. 73.3%, P=0.04), and the Ins allele frequency was significantly higher in patients (0.95 vs. 0.87, P=0.049, odds ratio=3.873). The Ins/Del genotype was associated with significantly higher TAC (P < 0.001) and lower MDA (P < 0.001) in patients than in controls.

Conclusion: Oxidative stress is markedly elevated in MI patients, with MDA serving as a robust biomarker. The CASP8 Ins/Ins genotype and Ins allele may increase MI susceptibility, while the Ins/Del genotype appears protective by enhancing antioxidant capacity. These findings suggest potential genetic markers for MI risk stratification.