Haplotype structure and functional genotype-phenotype interactions of PON1 (L55M/Q192R) variants in Egyptian children with nephrotic syndrome.

backgroundNephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, and dyslipidemia. Paraoxonase-1 (PON1), an HDL-associated antioxidant enzyme, contributes to lipid protection and redox homeostasis.

objectivesTo investigate the associations of PON1 L55M (rs854560) and Q192R (rs662) polymorphisms with NS and their relationships with PON1 concentrations in an Egyptian pediatric cohort. PATIENTS AND

methodsThis case-control study included 84 children aged 4-12 years: 42 with NS and 42 age- and sex-matched healthy controls. Serum PON1 concentration, lipid profile, albumin, blood urea, and urinary albumin excretion were assessed. PON1 polymorphisms were genotyped using tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR).

resultsChildren with NS had higher total cholesterol, LDL cholesterol, triglycerides, blood urea, and urinary albumin excretion, and lower HDL cholesterol, albumin, and PON1 concentrations than controls (all p < 0.001). The L55M MM genotype was more frequent in NS than controls (66.7% vs. 40.5%; OR = 3.77, p = 0.02) and was associated with an adverse biochemical profile. For Q192R, the R allele was associated with NS (61.9% vs. 42.9%; OR = 2.17, p = 0.01), while the RR genotype showed an association under the recessive model (OR = 2.67, p = 0.04). MM and RR carriers had the lowest PON1 concentrations. Haplotype analysis suggested associations between the LQ and MR haplotypes and NS.

conclusionsPON1 genetic variation and reduced PON1 concentrations may contribute to the metabolic phenotype and susceptibility to NS, supporting a potential role for PON1-mediated antioxidant pathways in disease pathophysiology and variation in oxidative stress responses among children.