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Replication analysis for severe diabetic retinopathy.

ABSTRACT: PURPOSE:The purpose of this study is to attempt to replicate the top single nucleotide polymorphism (SNP) associations from a previous genome-wide association study (GWAS) for the sight-threatening complications of diabetic retinopathy in an independent cohort of diabetic subjects from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). METHODS:This study included 469 type 1 diabetic, Caucasian subjects from WESDR. Cases (n = 208) were defined by prior laser treatment for either proliferative diabetic retinopathy or diabetic macular edema. Controls (n = 261) were all other subjects in the cohort. Three hundred eighty-nine SNPs were tested for association using the Illumina GoldenGate custom array. A retinopathy-only subanalysis was conducted in 437 subjects by removing those with end-stage renal disease. Evaluation for association between cases and controls was conducted by using chi-square tests. A combined analysis incorporated the results from WESDR with the prior GWAS. RESULTS:No associations were significant at a genome-wide level. The analysis did identify SNPs that can be pursued in future replication studies. The top association was at rs4865047, an intronic SNP, in the gene CEP135 (P value 2.06 × 10(-5)). The top association from the subanalysis was at rs1902491 (P value 2.81 × 10(-5)), a SNP that sits upstream of the gene NPY2R. CONCLUSIONS:This study nominates several novel genetic loci that may be associated with severe diabetic retinopathy. In order to confirm these findings, replication and extension in additional cohorts will be necessary as susceptibility alleles for diabetic retinopathy appear to be of modest effect.

SUBMITTER: Grassi MA

PROVIDER: S-EPMC3777289 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Replication analysis for severe diabetic retinopathy.

Grassi Michael A MA Tikhomirov Anna A Ramalingam Sudha S Lee Kristine E KE Hosseini S M SM Klein Barbara E K BE Klein Ronald R Lussier Yves A YA Cox Nancy J NJ Nicolae Dan L DL

Investigative ophthalmology & visual science 20120430 4

<h4>Purpose</h4>The purpose of this study is to attempt to replicate the top single nucleotide polymorphism (SNP) associations from a previous genome-wide association study (GWAS) for the sight-threatening complications of diabetic retinopathy in an independent cohort of diabetic subjects from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR).<h4>Methods</h4>This study included 469 type 1 diabetic, Caucasian subjects from WESDR. Cases (n = 208) were defined by prior laser treatme ...[more]

PMID: 22427569

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Project description:AIM:To establish and compare serum proteomic of diabetic retinopathy (DR) patients in various phases and discuss pathogenesis of DR so as to find out possible serum specific molecular markers for early diagnosis of DR. METHODS:Thirty-two subjects were divided into four groups: one group of eight type 2 diabetes mellitus (T2DM) patients without apparent DR (No-DR, NDR), one group of eight T2DM patients with non-proliferative diabetic retinopathy (NPDR), one group of eight T2DM patients with proliferative diabetic retinopathy (PDR) and one group of eight healthy volunteer participants. Two dimensional fluorescence difference gel electrophoresis (2D-DIGE) was applied to establish differential protein expression profiles in four groups. Matrix-assisted laser desorption/ionization time of flight tandem mass spectrometry (MALDI-TOF-TOF MS) was applied to identify mass spectrometry of differential proteins and analyze follow-up bioinformatics. RESULTS:2D-DIGE maps of serum protein were satisfactory obtained from NDR, NPDR, PDR and normal control groups. Twenty-six different proteins spots were screened (the volume ratio was >1.5 based on DeCyder software analysis). Twenty-four of them were verified and two of them were not. Fifteen proteins were verified. Most of them were high-abundant proteins in serum. The four relatively low-abundant ones were beta 2-glycoprotein I (?(2)-GPI), alpha2-HS-glycoprotein(AHSG), alpha1-acid glycoprotein(?(1)-AGP) and apolipoprotein A-1(apo A-1). ?(2)-GPI expression was gradually increased in the development of DR but unrelated to the severity of DR. The volume ratio of ?(2)-GPI is 1.54, 2.43, and 2.84 in NDR, NPDR and PDR group respectively compared with normal control group. CONCLUSION:Serum proteomic analysis of 2D-DIGE combined with MALDI-TOF-TOF MS is feasible to be applied in the study of DR. ?(2)-GPI probably takes part in the process of DR occurrence and development and it could be a candidate biomarker on DR diagnosis in early phase.

Project description:IntroductionThere is a high and ever-increasing global prevalence of diabetic retinopathy (DR) and invasive imaging techniques are often required to confirm the presence of proliferative disease. The aim of this study was to explore the images of a rapid and non-invasive technique, widefield optical coherence tomography angiography (OCT-A), to study differences between patients with severe non-proliferative and proliferative DR (PDR).MethodsWe conducted an observational longitudinal study from November 2022 to March 2023. We recruited 75 patients who were classified into a proliferative group (28 patients) and severe non-proliferative group (47 patients). Classification was done by specialist clinicians who had full access to any multimodal imaging they required to be confident of their diagnosis, including fluorescein angiography. For all patients, we performed single-shot 4 × 4 and 10 × 10 mm (widefield) OCT-A imaging and when possible, the multiple images required for mosaic 17.5 × 17.5 mm (ultra widefield) OCT-A imaging. We assessed the frequency with which proliferative disease was identifiable solely from these OCT-A images and used custom-built MATLAB software to analyze the images and determine computerized metrics such as density and intensity of vessels, foveal avascular zone, and ischemic areas.ResultsOn clinically assessing the OCT-A 10 × 10 fields, we were only able to detect new vessels in 25% of known proliferative images. Using ultra-widefield mosaic images, however, we were able to detect new vessels in 100% of PDR patients. The image analysis metrics of 4 × 4 and 10 × 10 mm images did not show any significant differences between the two clinical groups. For mosaics, however, there were significant differences in the capillary density in patients with PDR compared to severe non-PDR (9.1% ± 1.9 in the PDR group versus 11.0% ± 1.9 for severe group). We also found with mosaics a significant difference in the metrics of ischemic areas; average area of ischemic zones (253,930.1 ± 108,636 for the proliferative group versus 149,104.2 ± 55,101.8 for the severe group.ConclusionsOur study showed a high sensitivity for detecting PDR using only ultra-widefield mosaic OCT-A imaging, compared to multimodal including fluorescein angiography imaging. It also suggests that image analysis of aspects such as ischemia levels may be useful in identifying higher risk groups as a warning sign for future conversion to neovascularization.

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Replication analysis for severe diabetic retinopathy.

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Replication analysis for severe diabetic retinopathy.

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