The Role of GPX4 rs713041 Polymorphism in Hypertension Susceptibility Among Iraqi Patients

Abstract

Hypertension, a global health challenge and major contributor to cardiovascular disease, is influenced by both environmental and genetic factors. Among genetic regulators, the glutathione peroxidase 4 (GPX4) gene plays a critical role in antioxidant defense mechanisms, especially in lipid peroxidation and ferroptosis regulation. A functional single nucleotide polymorphism (SNP) in the 3′ untranslated region (3′UTR) of GPX4, rs713041 (C>T), has been linked to altered enzyme activity and increased oxidative stress. This study evaluated the association between GPX4 rs713041 polymorphism and hypertension in an Iraqi cohort, with emphasis on sex-specific effects and genetic models. A total of 45 hypertensive patients and 35 healthy controls aged 40–70 years were genotyped using TaqMan PCR assays. Results revealed that the TT and CT genotypes were more prevalent among hypertensive individuals, while the CC genotype was significantly more common in the control group. The T allele was associated with increased hypertension risk (63.33% in patients vs. 38.57% in controls; P = 0.001). Males with the TT genotype had a fivefold increased risk, while CC was protective. Under a dominant genetic model, individuals carrying at least one T allele (CT+TT) were nearly five times more likely to develop hypertension (OR = 4.9, P = 0.004). Additionally, GPX4 serum levels were significantly reduced in hypertensive patients and appeared to correlate with genotype. These findings suggest that the GPX4 rs713041 T allele is a genetic risk factor for hypertension in the Iraqi population, particularly among males. GPX4 polymorphism genotyping may serve as a potential biomarker for early identification of individuals at elevated risk.