Abstract

Amal Al-Eisa* Jalaja Sukumaran and Mohammad Z. Haider

Paraoxonase1 (PON1) is a serum enzyme bound to high density lipoproteins and has antioxidant as well as anti-atherogenic effects. Molecular studies of PON1 revealed two polymorphic sites at amino acids 55 and 192 resulting in two different allozymes. These allozymes result from L- genotype (leucine/high activity) and Mgenotype (Methionine /low activity) at residue 55 and A- (arginine/high activity) and B- (glutamine/low activity) at site 192 respectively. We have studied the association of Paraoxonase1 (PON1) gene polymorphisms with the histopathological types of idiopathic nephrotic syndrome (INS) in Kuwaiti Arab children. The PON1 gene, 55 and 192 polymorphisms were analyzed in 50 Kuwaiti children with INS and 50 healthy controls of a similar age, sex and ethnic background. The patients included 32 children with minimal change nephrotic syndrome (MCNS) and 18 with focal segmental glomerulosclerosis (FSGS). The PON1 gene polymorphisms were detected by using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) methods. The incidence of LL genotype (Leucine residue) was detected in 25/50 (50%) of the INS patients group compared to 24/50 (48%) in the controls (p = 0.84). The heterozygous genotype LM was detected in 21/50 (42%) in the INS patients compared to18/50 (36%) in the controls (p = 0.68). The homozygous MM-genotype (methionine residue) was detected in 4/50 (8%) INS patients compared to 8/50 (16%) in the controls (p = 0.35). The combined L-allele frequency in homozygous LL and the heterozygous subjects was 71% in INS patients compared to 66% in the controls (p = 0.54). The L-allele in both its homozygous LL and heterozygous LM genotype was found to be significantly more common in FSGS patients compared to MCNS patients (p = 0.0001) and also when compared to the controls (p = 0.0007). PON-1 gene, 192 polymorphism, the AA-genotype (glutamine residue) was uniformly detected in all patients and controls. Our data demonstrate a strong association between the L-allele of PON1 gene ‘55’ polymorphism and pathogenesis of FSGS in Kuwaiti Arab children with idiopathic nephrotic syndrome.