A genome‐wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes

Abstract

Purpose Diabetic retinopathy is the most common eye complication in patients with diabetes. The purpose of this study is to identify genetic factors contributing to severe diabetic retinopathy. Methods A genome-wide association approach was applied. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. Significant SNPs were taken forward for meta-analysis using multiple Caucasian cohorts. Results 560 cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a P value of 4.05 × 10-9. Two nearby SNPs, rs10765219 and rs11018670 also showed promising P values (P values = 7.41 × 10-8 and 1.23 × 10-8, respectively). In the meta-analysis using multiple Caucasian cohorts (excluding GoDARTS), rs10765219 and rs11018670 showed associations for diabetic retinopathy (P=0.003 and 0.007, respectively) while the P value of rs3913535 was not significant (P=0.429). Conclusion This genome-wide association study of severe diabetic retinopathy suggests new evidence for the involvement of the NOX4 gene.

General physicians role in stalling the progression of diabetic nephropathy and retinopathy

“…pol, povišen krvni pritisak, pušenje i gojaznost 5,12,13 . Kada je dijebetesna nefropatija u pitanju, pored navedenih faktora uticaj na razvoj i progresiju bolesti ima i hiperproteinska ishrana 3 .…”

“…Diabetic retinopathy is the most frequent singular cause of blindness among working people in Great Britain. 5 The estimated number of blind persons, due to diabetic retinopathy and maculopathy is 3.1% in Central and 4.9% in Eastern Europe. 6 Economic consequences, due to vision damage or total loss caused by diabetes are affecting the diseased and their family members, as well as, health systems and society as a whole.…”

“…3,8,9,10 Most risk factors for microvascular diabetic complications are common. 3,5 Beside genetic predisposition, the key factor in the development of diabetic nephropathy and retinopathy is chronic hyperglycemia. 3,5,11 Other risk factors for diabetic retinopathy are the duration of the disease, male gender, hypertension, smoking, and obesity.…”

“…3,5 Beside genetic predisposition, the key factor in the development of diabetic nephropathy and retinopathy is chronic hyperglycemia. 3,5,11 Other risk factors for diabetic retinopathy are the duration of the disease, male gender, hypertension, smoking, and obesity. 5,12,13 Same risk factors apply to diabetic nephropathy as well, with the addition of hyper protein nutrition.…”

CACNB2 Is a Novel Susceptibility Gene for Diabetic Retinopathy in Type 1 Diabetes

“…Family studies have further revealed that PDR clusters in families and our previous data suggested a significant genetic component in the pathogenesis of PDR that was as high as 52% ( 10 ). Nevertheless, only a few genetic risk factors have been robustly identified for PDR ( 11 – 14 ). Therefore, we performed linkage and association analyses in individuals with type 1 diabetes to identify novel susceptibility loci and genes predisposing to PDR and followed up the findings in retinal pigmented epithelial cells.…”