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A systematic meta-analysis of genetic association studies for diabetic retinopathy.

ABSTRACT: OBJECTIVE: Diabetic retinopathy is a sight-threatening microvascular complication of diabetes with a complex multifactorial pathogenesis. A systematic meta-analysis was undertaken to collectively assess genetic studies and determine which previously investigated polymorphisms are associated with diabetic retinopathy. RESEARCH DESIGN AND METHODS: All studies investigating the association of genetic variants with the development of diabetic retinopathy were identified in PubMed and ISI Web of Knowledge. Crude odds ratios (ORs) and 95% CIs were calculated for single nucleotide polymorphisms and microsatellite markers previously investigated in at least two published studies. RESULTS: Twenty genes and 34 variants have previously been studied in multiple cohorts. The aldose reductase (AKR1B1) gene was found to have the largest number of polymorphisms significantly associated with diabetic retinopathy. The z-2 microsatellite was found to confer risk (OR 2.33 [95% CI 1.49-3.64], P = 2 x 10(-4)) in type 1 and type 2 diabetes and z+2 to confer protection (0.58 [0.36-0.93], P = 0.02) against diabetic retinopathy in type 2 diabetes regardless of ethnicity. The T allele of the AKR1B1 promoter rs759853 variant is also significantly protective against diabetic retinopathy in type 1 diabetes (0.5 [0.35-0.71], P = 1.00 x 10(-4)), regardless of ethnicity. These associations were also found in the white population alone (P < 0.05). Polymorphisms in NOS3, VEGF, ITGA2, and ICAM1 are also associated with diabetic retinopathy after meta-analysis. CONCLUSIONS: Variations within the AKR1B1 gene are highly significantly associated with diabetic retinopathy development irrespective of ethnicity. Identification of genetic risk factors in diabetic retinopathy will assist in further understanding of this complex and debilitating diabetes complication.

SUBMITTER: Abhary S

PROVIDER: S-EPMC2731535 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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A systematic meta-analysis of genetic association studies for diabetic retinopathy.

Abhary Sotoodeh S Hewitt Alex W AW Burdon Kathryn P KP Craig Jamie E JE

Diabetes 20090708 9

<h4>Objective</h4>Diabetic retinopathy is a sight-threatening microvascular complication of diabetes with a complex multifactorial pathogenesis. A systematic meta-analysis was undertaken to collectively assess genetic studies and determine which previously investigated polymorphisms are associated with diabetic retinopathy.<h4>Research design and methods</h4>All studies investigating the association of genetic variants with the development of diabetic retinopathy were identified in PubMed and IS ...[more]

PMID: 19587357

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Project description:ImportancePrevious studies on the relationship between diabetic retinopathy (DR) and cardiovascular disease (CVD) focused on the early stages of DR. Understanding whether patients with type 2 diabetes and severe stages of DR (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]) have a higher risk of CVD will allow physicians to more effectively counsel patients.ObjectiveTo examine the association of severe stages of DR (DME and PDR) with incident CVD in patients with type 2 diabetes.Data sourcesEnglish-language publications were reviewed for articles evaluating the relationship of DR and CVD in MEDLINE, EMBASE, Current Contents, and the Cochrane Library from inception (January 1, 1950) to December 31, 2014, using the search terms diabetic retinopathy OR macular edema AND stroke OR cerebrovascular disease OR coronary artery disease OR heart failure OR myocardial infarction OR angina pectoris OR acute coronary syndrome OR coronary artery disease OR cardiomyopathy.Study selectionAmong 656 studies screened for eligibility, 7604 individuals were included from 8 prospective population-based studies with data on photographic-based DR grading, follow-up visits, and well-defined incident CVD end point.Data extraction and synthesisTwo independent reviewers conducted a systematic search of the 4 databases, and a single pooled database was developed. Incidence rate ratios (IRRs) were estimated for patients with DME, PDR, and vision-threatening DR, compared with persons without these conditions, by using individual participant data followed by a standard inverse-variance meta-analysis (2-step analysis). The review and analyses were performed from January 1, 2009, to January 1, 2017.Main outcome and measuresIncident CVD, including coronary heart disease, stroke, or death from cardiovascular causes.ResultsAmong 7604 patients with type 2 diabetes, the prevalence of DME was 4.6% and PDR, 7.4%. After a mean follow-up of 5.9 years (range, 3.2-10.1 years), 1203 incident CVD events, including 916 coronary heart disease cases, were reported. Persons with DME or PDR were more likely to have incident CVD (IRR, 1.39; 95% CI, 1.16-1.67) and fatal CVD (IRR, 2.33; 95% CI, 1.49-3.67) compared with those without DME or PDR.Conclusions and relevancePatients with type 2 diabetes and DME or PDR have an increased risk of incident CVD, which suggests that these persons should be followed up more closely to prevent CVD.

Project description:BACKGROUND: Transforming growth factor-beta (TGF-?1) gene has been regarded as an important mechanism in angiogenesis, endothelial cell proliferation, adhesion,and the deposition of extracellular matrix. The TGF-?1 gene may be involved in the development of diabetic retinopathy (DR) through disrupting angiogenesis. However, studies investigating the relationship between -509C/T and +869T/C(L10P) polymorphisms and DR yielded contradictory and inconclusive outcomes. In order to realize these ambiguous findings, a meta-analysis was performed to assess the association between the TGF-?1 gene polymorphisms and susceptibility to DR. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a search of all English reports on studies for the association between the TGF-?1 gene polymorphisms and susceptibility to DR using Medline, the Cochrane Library, EMbase, Web of Science, Google (scholar), and all Chinese reports were identified manually and on-line using CBMDisc, Chongqing VIP database, and CNKI database. The strict selection criteria and exclusion criteria were determined, and odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. The fixed or random effect model was selected based on the heterogeneity test among studies. Publication bias was estimated using Begg's funnel plots and Egger's regression test. RESULTS: A total of three studies were included in the meta-analysis and all included studies analyzed patients with type 2 diabetes. For +869T/C(L10P) polymorphism, significant association was observed in an allele model (L versus P: OR?=?1.34, 95%CI?=?1.03-1.73) and the recessive model (LL versus LP+PP: OR?=?1.70, 95%CI?=?1.13-2.56). As regards -509C/T polymorphism, no obvious associations were found for all genetic models. CONCLUSIONS: This meta-analysis suggested that the +869T/C(L10P) polymorphism in TGF?1 gene would be a potential protect factor for DR. However, the -509C/T polymorphism is not associated with DR.

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A systematic meta-analysis of genetic association studies for diabetic retinopathy.

Publications

A systematic meta-analysis of genetic association studies for diabetic retinopathy.

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