Predisposition of SOD1 , GPX1 , CAT genetic variants and their haplotypes in cataractogenesis of type 2 diabetes mellitus in Pakistan

Aims Cataract formation is accelerated by hyperglycemia due to the excessive production of oxidative stress. This study aimed to examine the underlaying role of glutathione peroxidase 1 ( GPX1 ) rs1800668, catalase ( CAT ) rs1001179 and superoxide dismutase 1 ( SOD1 ) 50 bp Indel promotor region variants in the pathogenesis of cataract in patients with diabetes. Methods A population-based case-control study of n =680 individuals was conducted which comprised of four respective groups: type 2 diabetes mellitus, diabetic cataract, senile cataract patients and controls. Screening of genotypes was performed by allele-specific (AS) and conventional polymerase chain reaction (PCR). Statistical testing was carried out using SPSS© 20.0, MedCal© and SNPStats© software’s. Bioinformatics analysis of linkage disequilibrium was done by HaploView© software 7.0. Results GPX1 (rs1800668) showed significant association with higher susceptibility of opacification in type 2 diabetes mellitus ( χ 2 =23.0, Adjusted OR=1.63, 95% CI: 1.05–2.49, p <0.001). A protective role was anticipated by CAT variant (rs1001179) for the development of resistance against the pathogenicity of cataract with diabetes ( χ 2 = 107, Adjusted OR=0.17, 95% CI: 0.10–0.29, p <0.001). Linkage disequilibrium (LD) plot of GPX1 and CAT variants revealed that CTC-CTT haplotypes demonstrated the presence of linkage (Dʹ=1.0) and co-inheritance (LOD=13.84) in patients of diabetic cataract. Conclusions GPX1 (rs1800668) variant may serve as an antioxidant biomarker for the assessment of risk for cataract in type 2 diabetes mellitus. GPX1 enzyme owed an antioxidant activity which can reduce the oxidative stress and hence could develop resistance in cataractogenesis. The findings could be beneficial as a potential target to the future pharmacogenomic studies of cataract prevention and eradication in diabetes mellitus.