Abstract
Background: The development of senile cataract is a multifactorial process with oxidative stress and its sequelae are clearly involved in its etiology. Cataract is also one of the earliest secondary complications of diabetes mellitus. Paraoxonase (PON) enzyme is an antioxidant High-Density Lipoprotein (HDL)-associated enzyme. In mammals, three genes of paraoxonase, PON1, PON2, and PON3, have been identified. Aim: To assess the contribution of PON1-55 and PON1-192 gene polymorphisms as risk factors for senile cataract formation among diabeticand non-diabetic Egyptian patients. Methods: 132 Egyptian cataract patients (66 without diabetes and 66 with diabetes) and 106 subjects with matched age and sex free of cataract and diabetes control subjects were included in the present study using multiplex PCR for PON1-55 and PON1-192 gene polymorphisms followed by restriction fragment length polymorphism analysis. Results: The study revealed that there was a significant difference in PON1-55 genotypes; LL, LM and MM (p=0.0001) and in PON1-192 genotypes; QQ, QR and RR (p=0.0001) genotypes distribution among cataract patients with and without diabetes and controls. Also there was a significant difference in L and M (p=0.003) and in Q and R allele frequencies (p=0.005) among cataract patients with and without diabetes and controls. In addition there was a significant difference in the distribution of 55 LM/192 RR combined genotypes with the highest frequency in cataract diabetic subgroup (75%), while 55LL/192RR, 55LL/192QR and 55LM/192QR combined genotypes showed the highest frequencies among the control group (52.4%, 59.1% and 66.7% respectively). Conclusion: For the first time, we provide evidence that functional polymorphisms in the PON1 gene may influence the risk of cataract in both non-diabetic and diabetic subgroups in Egyptian populations, suggesting new clues that help to clarify the pathogenesis of cataract.
Highlights
Cataract development is usually very slow or gradual process but in some cases it could occur rapidly and it generally affects both eyes [1,2]
The study revealed that there was a significant difference in Paraoxonase 1 (PON1)-55 genotypes; LL, LM and MM (p=0.0001) and in PON1-192 genotypes; QQ, QR and RR (p=0.0001) genotypes distribution among cataract patients with and without diabetes and controls
For the first time, we provide evidence that functional polymorphisms in the PON1 gene may influence the risk of cataract in both non-diabetic and diabetic subgroups in Egyptian populations, suggesting new clues that help to clarify the pathogenesis of cataract
Summary
Cataract development is usually very slow or gradual process but in some cases it could occur rapidly and it generally affects both eyes [1,2]. As oxidative events are of great importance in diabetic complications and, in the lens, they may have a role in the pathogenesis of cataract associated with diabetes mellitus [4]. Paraoxonase 1 (PON1) is a high-density lipoprotein-associated enzyme that is believed to be involved in the protection against oxidative stress. PON1, PON2, and PON3, have been identified in mammal [6]. The development of senile cataract is a multifactorial process with oxidative stress and its sequelae are clearly involved in its etiology. Paraoxonase (PON) enzyme is an antioxidant High-Density Lipoprotein (HDL)-associated enzyme. Three genes of paraoxonase, PON1, PON2, and PON3, have been identified
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