Association of PON2 and PON3 polymorphism with risk of developing cataract

Abstract

Purpose Paraoxonases (PON) are calcium bound enzymes offering protection against oxidative stress by working as endogenous free-radical scavenging molecules. Oxidative stress has been implicated in pathophysiology of many diseases including cataract. Lens opacity is an age related disorder which is a principal cause of blindness in Pakistani population. Relationship of PON2 and PON3 polymorphism with genetic predisposition for incidence of cataract has not been investigated till date. Objective of the current study was to explore possible association between PON2 and PON3 polymorphism with incidence of cataract in local population. Methods Our study design comprised of fifty-one cataractous and fifty-nine healthy individuals. Identification of single nucleotide polymorphism (SNP) at positions (C311S and G148A) for PON2 and C133A for PON3 was conducted using restriction fragment length polymorphism (RFLP). Results Statistical analysis revealed significant association of PON2 G148 allele with incidence of cataract. GG allele was found to be higher in cataract patients as compared to control ( p < 0.001) suggesting distribution of PON2 G148A genotype and allele frequency is linked with cataractogenesis. There was no noticeable association between PON2 C311S and PON3 C133A. Significant difference was observed in distribution of 311CS/148A combined genotype with highest frequency in control individuals (88.89%), while 311S/148G combined genotypes showed the highest frequencies among the cataract patients (71.42%). Conclusion Our data suggests mutation at G148A might be related with incidence of cataract in studied population.

Human Paraoxonase-2 (PON2): Protein Functions and Modulation

“…A combined genotype analysis for PON2 polymorphisms revealed that the combination of G148 and S311 was more frequent in cataract subjects, whereas heterogeneous alleles at 311 and 148 were more likely to be present in subjects without lens opacity. It seems likely that the presence of mutations at 148 and 311 positions might be considered as a risk factor for the development of cataracts [48]. The PON2 gene polymorphisms A148G and S311C have been independently associated with diabetic nephropathy in type II diabetic patients.…”

Paraoxonase 2 Deficiency Causes Mitochondrial Dysfunction in Retinal Pigment Epithelial Cells and Retinal Degeneration in Mice

“…Ala/Gly at position 148 and Ser/Cys at position 311 are two of the polymorphisms of PON2 that are often detected [26] and these polymorphisms are associated with its decreased lactonase activity [34]. It appears likely that the existence of mutations at the 148 and 311 sites could be regarded as a risk factor for the onset of cataracts [35]. The PON2 gene polymorphisms A148G and S311C have been independently linked to diabetic nephropathy in type II diabetic patients [36].…”