IMPACT OF PON1 GENETIC DIVERSITY ON DIABETIC DYSLIPIDEMIA IN IRAQI PATIENTS

Abstract

Background: Diabetic dyslipidemia is a major contributor to cardiovascular complications in type 2 diabetes mellitus (T2DM). Paraoxonase-1 (PON1), an HDL-associated antioxidant enzyme, protects lipoproteins from oxidative modification, and genetic polymorphisms may influence its activity and susceptibility to dyslipidemia. Aim: To investigate the association of PON1 polymorphisms (rs662, rs854571, and rs854572) with diabetic dyslipidemia in Iraqi patients with T2DM. Methods: A case–control study comprising 150 type 2 diabetic patients with dyslipidemia and 150 without. Serum glucose, lipid profile, and PON1 concentrations were measured using standard biochemical methods and ELISA. Genotyping was performed by allele-specific polymerase chain reaction. Results: Patients with dyslipidemia exhibited significantly elevated fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TCH), and low-density lipoprotein (LDL-C), but lower high-density lipoprotein (HDL-C), PON1 concentrations, and HDL functional index than controls. The rs662 C/C genotype was associated with increased risk of dyslipidemia (OR = 2.63, p = 0.015), while the rs854571 C/C and rs854572 variant genotypes also conferred significant susceptibility. Linkage Disequilibrium (LD) analysis demonstrated weak correlations among the investigated loci. Haplotype analysis identified the CTC haplotype as significantly associated with dyslipidemia (OR = 2.49, p = 0.041). Conclusions: PON1 genetic variation, particularly rs662, contributes to diabetic dyslipidemia in Iraqi patients. Combined haplotype analysis provides additional evidence that PON1 genetic diversity influences lipid homeostasis and may help identify individuals at increased cardiovascular risk.