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A Systematic Meta-Analysis of Genetic Association Studies for Diabetic Retinopathy

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 dia...

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Autores principales: Abhary, Sotoodeh, Hewitt, Alex W., Burdon, Kathryn P., Craig, Jamie E.
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731535/
https://www.ncbi.nlm.nih.gov/pubmed/19587357
http://dx.doi.org/10.2337/db09-0059
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author Abhary, Sotoodeh
Hewitt, Alex W.
Burdon, Kathryn P.
Craig, Jamie E.
author_facet Abhary, Sotoodeh
Hewitt, Alex W.
Burdon, Kathryn P.
Craig, Jamie E.
author_sort Abhary, Sotoodeh
collection PubMed
description 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 micro satellite was found to confer risk (OR 2.33 [95% CI 1.49–3.64], P = 2 × 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 × 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.
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spelling pubmed-27315352010-09-01 A Systematic Meta-Analysis of Genetic Association Studies for Diabetic Retinopathy Abhary, Sotoodeh Hewitt, Alex W. Burdon, Kathryn P. Craig, Jamie E. Diabetes Original Article 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 micro satellite was found to confer risk (OR 2.33 [95% CI 1.49–3.64], P = 2 × 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 × 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. American Diabetes Association 2009-09 2009-07-08 /pmc/articles/PMC2731535/ /pubmed/19587357 http://dx.doi.org/10.2337/db09-0059 Text en © 2009 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Article
Abhary, Sotoodeh
Hewitt, Alex W.
Burdon, Kathryn P.
Craig, Jamie E.
A Systematic Meta-Analysis of Genetic Association Studies for Diabetic Retinopathy
title A Systematic Meta-Analysis of Genetic Association Studies for Diabetic Retinopathy
title_full A Systematic Meta-Analysis of Genetic Association Studies for Diabetic Retinopathy
title_fullStr A Systematic Meta-Analysis of Genetic Association Studies for Diabetic Retinopathy
title_full_unstemmed A Systematic Meta-Analysis of Genetic Association Studies for Diabetic Retinopathy
title_short A Systematic Meta-Analysis of Genetic Association Studies for Diabetic Retinopathy
title_sort systematic meta-analysis of genetic association studies for diabetic retinopathy
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731535/
https://www.ncbi.nlm.nih.gov/pubmed/19587357
http://dx.doi.org/10.2337/db09-0059
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