Genetics of Diabetic Retinopathy

Uhlmann, Katja; Kovacs, Peter; Boettcher, Yvonne; Hammes, HP; Paschke, Ralf

doi:10.1055/s-2006-924260

Cited by 70 publications

(41 citation statements)

References 103 publications

(101 reference statements)

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“…Three genome-wide scans have offered suggestive evidence of linkage, though on a number of different chromosomes in patients with type 2 diabetes (19 -21). The associations to various biologically relevant candidate genes have been extraordinarily difficult to replicate (22). Such results are typical for multifactorial diseases with only a moderate familiality.…”

Section: Discussionmentioning

confidence: 99%

Heritability of Proliferative Diabetic Retinopathy

Hietala

Forsblom²,

Summanen³

et al. 2008

Diabetes

154

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on behalf of the FinnDiane Study Group OBJECTIVE-Diabetic nephropathy clusters in families, suggesting that genetic factors play a role in its pathogenesis. We investigated whether similar clustering exists for proliferative retinopathy in families with two or more siblings with type 1 diabetes. RESEARCH DESIGN AND METHODS-TheFinnDiane Study has characterized 20% (4,800 patients) of adults with type 1 diabetes in Finland. In 188 families, there were at least two siblings with type 1 diabetes. Ophthalmic records were obtained for 369 of 396 (93%) and fundus photographs for 251 of 369 (68%) patients. Retinopathy was graded based on photographs and/or repeated ophthalmic examinations using the Early Treatment of Diabetic Retinopathy grading scale.RESULTS-Mean age at onset of diabetes was 14.3 Ϯ 10.2 years, and mean duration was 25.9 Ϯ 11.8 years. Proliferative retinopathy was found in 115 of 369 patients (31%). The familial risk of proliferative retinopathy was estimated in 168 of 188 sibships, adjusted for A1C, duration, and mean blood pressure. Proliferative retinopathy in the probands (48 of 168) was associated with an increased risk (odds ratio 2.76 [95% CI 1.25-6.11], P ϭ 0.01) of proliferative retinopathy in the siblings of probands (61 of 182). The heritability of proliferative retinopathy was h 2 ϭ 0.52 Ϯ 0.31 (P Ͻ 0.05). After 20 years of diabetes, almost all patients with type 1 diabetes and 58% of patients with type 2 diabetes show signs of retinopathy. When retinopathy worsens, severe visual loss eventually threatens 5-10% of patients (2). The most severe form of retinopathy is proliferative retinopathy, and most of the patients with this complication will become blind after 5-10 years without treatment (3). The prevalence of proliferative retinopathy varies between 13 and 50% after 15-20 years of diabetes duration in patients needing insulin (2,4). CONCLUSIONS-WeThe prevalence of any retinopathy is strongly related to duration and glucose exposure (2,4). Furthermore, poor glycemic control increases the incidence and progression of retinopathy (5,6). Nevertheless, glycemic exposure seems to explain only a part of the risk of proliferative retinopathy (7). In patients with type 2 diabetes, high blood pressure increases the incidence of retinopathy (8). It is noteworthy that proliferative retinopathy is associated with diabetic nephropathy, a complication that is at least in part genetically determined (2). Such an association suggests that familial factors may also contribute to the development of proliferative retinopathy.Therefore, the aim of this study was to elucidate whether there is a familial clustering of proliferative retinopathy in patients with longstanding type 1 diabetes and to estimate the degree of familiality by calculating the heritability of proliferative retinopathy. RESEARCH DESIGN AND METHODSThe present study was undertaken as part of the ongoing FinnDiane Study (Finnish Diabetic Nephropathy Study), a nationwide multicenter project with the aim of identifying genetic and environmenta...

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Section: Discussionmentioning

confidence: 99%

Heritability of Proliferative Diabetic Retinopathy

Hietala

Forsblom²,

Summanen³

et al. 2008

Diabetes

154

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“…This might be explained by the fact that HbA 1c fails to reflect the magnitude of acute glycaemic fluctuations, which may foster a pro-oxidative state [17]. In addition, genetically determined factors appear to influence susceptibility to diabetic retinopathy [18], which possibly involves polymorphic variations in genes that govern the generation of, or protection from, oxidative damage [19,20]. These findings have important clinical implications and suggest that it may be beneficial to monitor oxidative stress in concert with HbA 1c to identify subgroups of diabetic patients at high risk of initiation and progression of retinopathy.…”

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confidence: 99%

Evaluation of N ε-(3-formyl-3,4-dehydropiperidino)lysine as a novel biomarker for the severity of diabetic retinopathy

et al. 2008

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Aims/hypothesis Recent studies suggest that oxidative stress should be monitored alongside HbA 1c to identify subgroups of diabetic patients at high risk of initiation or progression of retinopathy. The acrolein-derived advanced lipoxidation end-product (ALE), N " -(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine), is a useful biomarker that reflects the cumulative burden of oxidative stress over long periods of time. The purpose of the present study was to investigate whether serum and haemoglobin levels of FDP-lysine are associated with the severity of diabetic retinopathy in type 1 and type 2 diabetic patients. Methods Serum and haemoglobin levels of FDP-lysine were measured by competitive ELISA in 59 type 1 and 76 type 2 diabetic patients with no retinopathy, non-proliferative retinopathy or proliferative retinopathy (mean age [±SEM] 54.3±1.3 years), and in 47 non-diabetic control individuals (mean age 51.9±2.1 years).Results Serum and haemoglobin levels of FDP-lysine were significantly increased in diabetic patients compared with control individuals (p=0.04 and p=0.002, respectively). However, no significant association was found between levels of serum FDP-lysine and the severity of diabetic retinopathy (p=0.97). In contrast, increased haemoglobin FDP-lysine levels were observed in patients with proliferative retinopathy compared with patients without retinopathy and with non-proliferative retinopathy (p=0.04). The relationship of FDP-lysine with proliferative retinopathy was unaltered after adjustment for HbA 1c , or other clinical parameters. Conclusions/interpretation Our data suggest that haemoglobin FDP-lysine may provide a useful risk marker for the development of proliferative diabetic retinopathy independently of HbA 1c , and that elevated intracellular ALE formation may be involved in the pathogenesis of this sight-threatening complication of diabetes.

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“…Additionally, WHO added diabetic retinopathy to the priority list of eye disease as it can be partly prevented and treated. It is a well-known fact that diabetes mellitus is a risk factor for cardiovascular disease [1][2][3]. Poor glycemic control and longer disease duration are leading cause to the development of angiopathic complications.…”

Section: Introductionmentioning

confidence: 99%

Association 0f Gpx-198C/T Gene Polymorphism (rs1050450-198C/T) in Sudanese with Diabetic Retinopathy

Nmn¹,

Ea²,

Am³

et al. 2017

J Blood Lymph

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Background: Diabetic retinopathy is the common micro-vascular complication of diabetes mellitus. It is the main cause of blindness among young adults worldwide. Poor glycemic control in addition to longer diabetic duration is the main risk factors for diabetic retinopathy. Many genes have been postulated as candidates for diabetic retinopathy. Little is known about anti-oxidative enzyme gene polymorphism and its association with diabetic retinopathy, mainly for catalase enzyme and manganese superoxide dismutase and glutathone genes. The study aims to assess the role of glutathone GPX-198C/T (rs1050450) gene polymorphism in diabetic retinopathy Sudanese patients and its relation with GPX level. In addition to determine the association of FBS, HbA1c and lipid in the pathogenesis of diabetic retinopathy. Methodology:The number of subjects involved were 130 which were classified into (n 60) clinically diagnosed as diabetic retinopathy and (n 70) diabetes mellitus without retinopathy as control group, age ranged from 22 to 80 years old, from Makkah Eye Complex. DNA was extracted and PCR product for GPX, gene segment were digested by Aba1 enzymes, moreover gene polymorphisms were determined. Serum GPX, activity and FBS, TG, CHOL and HbA1c level were analyzed using Cobas Int 400 using absorption photometer and immunoassay methods respectively. Results:The results revealed that, retinopathy is common in female than male by approximately 2 fold =1.9:1. Type II is more common in our population that type 1. The majority of the patients had type II diabetes (128, 98.5%) and only 2(1.5%) patients were type I diabetes mellitus. The activity of GPX, was significantly higher in DNR when compared with DR (p=0.003). Mean HbA1c and FBG concentration were significantly higher among DR than DNR p=0.001 and p=0.001 respectively. In contrast, mean serum CHOL and TG level revealed insignificant differences when compared DR with DNR. The genotyping for GPX-198C/T showed that, the frequency of CC was observed in 33(47%) in control higher than cases 13(22%), theses Associations for CCs, GPX-198C/T SNP rs1050450, decreased risk after correction for multiple testing (OR=0.310, 95% CI=0.176-0.486, p=0.001), While TT genotype was detected in 25(42%) cases and only 14(20%) in controls, these Associations for SNPs, TTs, GPX-198C/T SNP rs1050450, increased risk after correction for multiple testing (OR=2.4, 95% CI=1.10-5.90, p=0.004). The frequency of the allele C protective allele was found to be 48% among cases group while allele T-risky allele was higher among cases group 72%, OR=0.357 (0.216-0.433), p=0.001. Conclusion:The study concludes that there is a significant association between GPX-198C/T (rs1050450) gene polymorphism and the occurrence of diabetic retinopathy in Sudanese population. There is a significant decrease in GPX levels and glycemic control in patients with the mutant allele T. complications as retinopathy [6,7]. ROS reactive oxygen species are most common processes to develop vascular complications. Journal of Blood...

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Genetics of Diabetic Retinopathy

Cited by 70 publications

References 103 publications

Heritability of Proliferative Diabetic Retinopathy

Heritability of Proliferative Diabetic Retinopathy

Evaluation of N ε-(3-formyl-3,4-dehydropiperidino)lysine as a novel biomarker for the severity of diabetic retinopathy

Association 0f Gpx-198C/T Gene Polymorphism (rs1050450-198C/T) in Sudanese with Diabetic Retinopathy

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