Genetic susceptibility of diabetic retinopathy (original) (raw)

2008, Current Diabetes Reports

Diabetes continues to be a major source of morbidity and mortality among working-age adults nationally and internationally. The microvascular complications of diabetes, including diabetic retinopathy, account for a major proportion of disease-associated morbidity and likely contribute to macrovascular complications. Although glycemic control contributes to susceptibility for diabetic complications, some people with strict control develop these complications, whereas others with poor control remain complication free. This suggests a genetic contribution to disease development. Although many genes and proteins of vascular growth have been studied in association with diabetic retinopathy, no definitive major predisposing genes or functional consequences of genetic variants have been identified for microvascular complications of the disease. In this article, we review the studies done on candidate genes.

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Candidate gene studies of diabetic retinopathy in human

Molecular biology reports, 2016

Diabetic retinopathy (DR) is a multifactorial disease with complex pathophysiology. It is the main cause of blindness among the people in productive age. The purpose of this literature review is to highlight recent achievements in the genetics of diabetic retinopathy with particular focus on candidate gene studies. We summarized most of the available published data about candidate genes for diabetic retinopathy with the goal to identify main genetic aspects. We conclude that genetic studies reported contradictory findings and no genetic variants meet criteria of a diagnostic marker, or significantly elucidate the root of DR development. Based on these findings it is important to continue with the research in the field of DR genetics, mainly due to the fact that currently new possibilities and approaches associated with utilization of next-generation sequencing are available.

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Identifying Genetic Risk Factors for Diabetic Macular Edema and the Response to Treatment

Journal of Diabetes Research, 2020

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). DR is complex and the term encompasses several clinical subtypes of diabetic eye disease, including diabetic macular edema (DME), the most frequent cause of central vision loss in DR patients. Both genetic and environmental factors contribute to the pathophysiology of DR and its subtypes. While numerous studies have identified several susceptibility genes for DR, few have investigated the impact of genetics on DME susceptibility. This review will focus on the current literature surrounding genetic risk factors associated with DME. We will also highlight the small number of studies investigating the genetics of response to antivascular endothelial growth factor (anti-VEGF) injection, which is used to treat DME.

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Progress and challenges in genome-wide studies to understand the genetics of diabetic retinopathy

Annals of Eye Science, 2018

There are many advantages to understanding the genetics of human disease. Genetic markers can be used to calculate the risk of developing a disease, and elucidation of genetic risk factors can pinpoint the molecular aetiology of disease, which can facilitate the development of targeted therapies. Diabetic retinopathy (DR) is a common complication of diabetes that has a significant impact on quality of life. It has a clear genetic component, but determination of the genetic risk factors has proven difficult. To date, genome-wide studies for DR have been conducted on relatively small patient cohorts compared to other complex eye diseases and replication of genetic findings has been limited. The disease is highly heterogeneous, confounding attempts to classify patients into appropriate groups for genetic analysis and making direct comparisons between studies challenging. Future studies to determine the genetic causes of DR will need to focus on larger sample sizes, detailed phenotyping and appropriate classification of patients. Global co-operation and meta-analyses combining data from multiple studies will be critical to the discovery of genetic risk loci for DR.

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The association of previously reported polymorphisms for microvascular complications in a meta-analysis of diabetic retinopathy

Human genetics, 2015

We investigated the association of signals from previous GWAS and candidate gene meta-analyses for diabetic retinopathy (DR) or nephropathy (DN), as well as an EPO variant in meta-analyses of severe (SDR) and mild diabetic retinopathy (MDR). Meta-analyses of SDR (≥severe non-proliferative diabetic retinopathy (NPDR) or history of panretinal photocoagulation) and MDR (≥mild NPDR), defined based on seven-field stereoscopic fundus photographs, were performed in two well-characterized type 1 diabetes (T1D) cohorts: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC, n = 1,304) and Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR, n = 603). Among 34 previous signals for DR, after controlling for multiple testing, no association was replicated in our meta-analyses. rs1571942 and rs12219125 at PLXDC2 locus showed nominally significant (<0.05) association with SDR in the same direction as previous report, as did rs...

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Local and genetic determinants of vascular endothelial growth factor expression in advanced proliferative diabetic retinopathy

Molecular vision, 2008

In proliferative diabetic retinopathy (PDR) and other angiogenesis-associated diseases, increased levels of cytokines, inflammatory cells, growth factors, and angiogenic factors are present. Vascular endothelial growth factor (VEGF) appears to play a central role in mediating microvascular pathology in PDR. The purpose of the present study was to search for the association between the -634 C/G polymorphism of the VEGF gene and PDR. Moreover, it was hoped to determine whether serum and vitreous levels of VEGF are affected by genetic factors. This cross-sectional case-control study enrolled 349 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus. The case group consisted of 206 patients with an advanced form of PDR and for whom vitrectomy was performed, and the control group had 143 patients who had no clinical signs of diabetic retinopathy but did have type 2 diabetes of more than 10 years duration. To analyze the genotype distribution we had to compare the genotype...

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