DNA Repair Enzyme XRCC4 30 bp Indel Intron 3 Locus Significant Association with Predisposition of Cataract in Senility.

Impaired DNA damage repair cascade can disrupt the lens transparency due to aging-associated oxidative stress. The aim of study was to assess the association of 30 bp indel mutation (rs28360071) in XRCC4 gene with susceptibility of cataract in senility. The study followed case-control design with a total of n = 200 participants and divided equally into senile cataract patients and control groups. Conventional polymerase chain reaction (PCR) was performed for the genotyping of XRCC4 (rs28360071) mutation. In statistical measures, SPSS ® 20.0 software, MedCal©, and SNPStats© tools were used for data analysis. Distribution of homozygous D/D and mutant D allele was higher in senile cataract patients in comparison to controls. XRCC4 (rs28360071) mutation was significantly associated with predisposition senile cataract (χ2 = 13.96, adjusted OR = 2.29, 95% CI: 1.5-3.4, p < 0.001). Codominant model was suggested to be a best fit model. Mutant D/D genotype described significant association with LDL (adjusted OR = 1.67, 95% CI: 0.14-1.45, p = 0.03),and HDL (adjusted OR = 1.66, 95% CI: 0.92-2.31, p = 0.05) cholesterol with higher risk of senile cataract. XRCC4 (rs28360071) mutation may serve as a potential biomarker for the prognosis of cataract in senility. It can used to measure interruption in NHEJ repair pathway to indicate DNA damage in lens epithelial cells which could accelerate cataractogenesis with aging.

Clinical Association of Biochemical Variations Among Multilocus Genotypes of Antioxidant Enzymes with Susceptibility of Cataract in Hyperglycemia.

Hyperglycemia plays a pronounced role in accelerating the process of aging due to high oxidative stress which triggers dyslipidemia and subsequently led to the progression of cataract. The aim of this study was to investigate lipid profile and its relationship with genotypes of SOD1, GPX1, and CAT variants in cataract patients. Total n = 680 samples were screened in four groups: senile cataract (SC), diabetic cataract (DC), type 2 diabetes mellitus (DM), and controls (CL). Lipid profile was estimated and compared between groups, and its correlation was tested with glycemic markers. Association of SOD1 50 bp Indel, GPX1 (rs1800668), and CAT (rs1001179) genotypes with all clinical variables was investigated in cataract groups by regression statistics in SPSS® 16.0. Comparative analysis revealed that amount of total cholesterol and low-density lipoprotein parameters were significantly higher in both groups of cataracts when compared with controls (p < 0.01). Statistically higher levels of triglycerides were also evident in DM patients as compared with other three groups (p < 0.01). Significant weak positive correlation of glycated hemoglobin, fasting (FBG), and random blood glucose (RBG) levels was observed with triglycerides in DM (r = 0.16), SC (r = 0.15), and DC (r = 0.18) groups. Mutant genotype of SOD1 and CAT variants indicated significant association with TC, whereas GPX1 variant with FBG levels in accelerating predisposition of cataract in patients with diabetes (OR > 1.0). Outcomes suggested that TG may serve as a potential biomarker of lipid profile with manifestation of cataract in type 2 DM. Furthermore, hypercholesterolemia and hypertriglyceridemia demonstrated an inducing role in the pathogenesis of cataract with aging in hyperglycemia.

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 (χ2=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 (χ2 = 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 (D'=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.