Paraoxonase 1 Gene Polymorphism and Its Influence on Cardiovascular Threat in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is often complicated by oxidative stress, lipid abnormalities, and a high cardiovascular disease burden. This review aims to examine the effects of paraoxonase 1 (PON1) gene polymorphisms and its antioxidant activity in relation to high-density lipoproteins and the risk of cardiovascular diseases, such as atherosclerosis and coronary artery disease, in patients with T2DM. The published literature was comprehensively reviewed, focusing on studies exploring genetic variants of PON1, enzymatic activity levels, ethnic distribution, and their interaction with metabolic and environmental factors in diabetic populations. The findings consistently showed that reduced PON1 activity is a major determinant of vascular risk in T2DM. Genetic variations alter enzyme function: the R allele of Q192R enhances paraoxon hydrolysis but reduces the protection of low-density lipoproteins, whereas the M allele of L55M decreases protein stability and circulating concentration. These effects vary across populations, with significant ethnic differences in allele prevalence. Beyond genetics, lifestyle and dietary factors, such as intake of saturated fats or polyphenol-rich foods, modulate PON1 activity, highlighting important gene-environment interactions. PON1 polymorphisms play a pivotal role in shaping cardiovascular vulnerability in patients with T2DM. Measuring enzyme activity may serve as a more accurate predictor of cardiovascular disease risk than genotyping alone because it reflects both inherited and environmental influences. Integrating genetic profiling with personalised dietary, lifestyle, and therapeutic interventions may lead to more precise cardiovascular risk assessment and improved outcomes for patients with diabetes. This approach offers a promising direction for future research and clinical practice.