Association of PON1 Q192R/L55M Polymorphisms and Paraoxonase-1 levels with cardiometabolic risk in patients with type-2 diabetes mellitus.
To investigate the distribution of PON1 Q192R and L55M polymorphisms and serum PON1 concentration in Saudi patients with T2DM and to evaluate their associations with biochemical parameters and diabetes-related complications.
In this case-control study, 220 patients with T2DM and 120 healthy controls were enrolled from several hospitals in Madinah, KSA, from May 1, 2025 to December 15, 2025. Clinical and biochemical assessments included fasting plasma glucose (FPG), HbA1c, lipid profile, apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). PON1 Q192R and L55M genotypes were determined using PCR-RFLP, and serum PON1 concentration was measured by ELISA. Associations between genotypes, PON1 levels, metabolic indices, and diabetic complications were analyzed.
Serum PON1 levels were significantly lower in patients with T2DM compared with controls (p < 0.001). The genotype and allele frequencies of PON1 Q192R and L55M polymorphisms did not differ significantly between groups (p=0.18); Q192R allele: (p=0.21); L55M genotype: (p=0.58); L55M allele: (p=0.43). While neither polymorphism was associated with T2DM susceptibility, the Q192R variant was significantly associated with cardiovascular disease among patients with T2DM (p = 0.04). Both polymorphisms were significantly associated with serum PON1 concentration and glycemic indices (FPG and HbA1c; p < 0.05), whereas no significant associations were observed with BMI or lipid parameters.
In Saudi patients with T2DM, PON1 levels are notably lower, indicating reduced antioxidant defense. Although certain genetic polymorphisms of PON1 do not affect diabetes susceptibility, the Q192R variant may increase cardiovascular risks in T2DM, suggesting its role as a biomarker for cardiometabolic risk rather than disease development.
In this case-control study, 220 patients with T2DM and 120 healthy controls were enrolled from several hospitals in Madinah, KSA, from May 1, 2025 to December 15, 2025. Clinical and biochemical assessments included fasting plasma glucose (FPG), HbA1c, lipid profile, apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). PON1 Q192R and L55M genotypes were determined using PCR-RFLP, and serum PON1 concentration was measured by ELISA. Associations between genotypes, PON1 levels, metabolic indices, and diabetic complications were analyzed.
Serum PON1 levels were significantly lower in patients with T2DM compared with controls (p < 0.001). The genotype and allele frequencies of PON1 Q192R and L55M polymorphisms did not differ significantly between groups (p=0.18); Q192R allele: (p=0.21); L55M genotype: (p=0.58); L55M allele: (p=0.43). While neither polymorphism was associated with T2DM susceptibility, the Q192R variant was significantly associated with cardiovascular disease among patients with T2DM (p = 0.04). Both polymorphisms were significantly associated with serum PON1 concentration and glycemic indices (FPG and HbA1c; p < 0.05), whereas no significant associations were observed with BMI or lipid parameters.
In Saudi patients with T2DM, PON1 levels are notably lower, indicating reduced antioxidant defense. Although certain genetic polymorphisms of PON1 do not affect diabetes susceptibility, the Q192R variant may increase cardiovascular risks in T2DM, suggesting its role as a biomarker for cardiometabolic risk rather than disease development.
Authors
Ahmed Ahmed, Al-Nakhle Al-Nakhle, Ashour Ashour, Aljohani Aljohani, Eltahir Eltahir
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