Abstract
PurposeDiabetic 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.MethodsA 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 Single Nucleotide Polymorphisms (SNPs) were taken forward for meta‐analysis using multiple Caucasian cohorts.ResultsFive hundred and sixty 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).ConclusionThis genome‐wide association study of severe diabetic retinopathy suggests new evidence for the involvement of the NOX4 gene.
Highlights
Diabetic retinopathy (DR) is a chronic, progressive, potentially sight-threatening disease of the retinal microvasculature associated with pathophysiological changes intensified by diabetes
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
In the GoDARTS population, we identified 560 unrelated severe DR patients (133 individuals with severe background retinopathy and 427 individuals with proliferative diabetic retinopathy (PDR)) and 4106 controls (1873 individuals with no DR and 2233 individuals with mild background retinopathy) based on our definitions
Summary
Diabetic retinopathy (DR) is a chronic, progressive, potentially sight-threatening disease of the retinal microvasculature associated with pathophysiological changes intensified by diabetes It is the most common eye complication in diabetic patients and the most common cause of blindness among people of working age in the UK (Bunce & Wormald 2008). It is estimated that over 1000 new cases of blindness are caused by DR each year in England alone and a further 4000 people each year in the country are thought to be at risk of vision loss due to retinopathy (www.diabetes.co.uk 2017). In addition to the fact that there is a huge cost difference depending on the severity of DR, It has been estimated that without treatment for PDR, 50% of all patients will become blind within 5 years following diagnosis (Williams et al 2004). It is essential to identify and treat this disorder at an early stage and slow or stop its progress
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