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A genome-wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes.
Meng, Weihua; Shah, Kaanan P; Pollack, Samuela; Toppila, Iiro; Hebert, Harry L; McCarthy, Mark I; Groop, Leif; Ahlqvist, Emma; Lyssenko, Valeriya; Agardh, Elisabet; Daniell, Mark; Kaidonis, Georgia; Craig, Jamie E; Mitchell, Paul; Liew, Gerald; Kifley, Annette; Wang, Jie Jin; Christiansen, Mark W; Jensen, Richard A; Penman, Alan; Hancock, Heather A; Chen, Ching J; Correa, Adolfo; Kuo, Jane Z; Li, Xiaohui; Chen, Yii-der I; Rotter, Jerome I; Klein, Ronald; Klein, Barbara; Wong, Tien Y; Morris, Andrew D; Doney, Alexander S F; Colhoun, Helen M; Price, Alkes L; Burdon, Kathryn P; Groop, Per-Henrik; Sandholm, Niina; Grassi, Michael A; Sobrin, Lucia; Palmer, Colin N A.
Afiliação
  • Meng W; Division of Population Health Sciences, Medical Research Institute, Ninewells Hospital and School of Medicine, University of Dundee, Dundee, UK.
  • Shah KP; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois, USA.
  • Pollack S; Department of Epidemiology, Harvard T.H., Chan School of Public Health, Boston, Massachusetts, USA.
  • Toppila I; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
  • Hebert HL; Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • McCarthy MI; Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
  • Groop L; Division of Population Health Sciences, Medical Research Institute, Ninewells Hospital and School of Medicine, University of Dundee, Dundee, UK.
  • Ahlqvist E; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, UK.
  • Lyssenko V; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Agardh E; Oxford NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, UK.
  • Daniell M; Department of Clinical Sciences, Faculty of Medicine, Lund University, Malmo, Sweden.
  • Kaidonis G; Department of Clinical Sciences, Faculty of Medicine, Lund University, Malmo, Sweden.
  • Craig JE; Department of Clinical Sciences, Faculty of Medicine, Lund University, Malmo, Sweden.
  • Mitchell P; Department of Clinical Sciences, Faculty of Medicine, Lund University, Malmo, Sweden.
  • Liew G; Department of Ophthalmology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
  • Kifley A; Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
  • Wang JJ; Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
  • Christiansen MW; Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney C24, Sydney, Australia.
  • Jensen RA; Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney C24, Sydney, Australia.
  • Penman A; Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney C24, Sydney, Australia.
  • Hancock HA; Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney C24, Sydney, Australia.
  • Chen CJ; Cardiovascular Health Research Unit, School of Medicine, University of Washington, Seattle, Washington, USA.
  • Correa A; Cardiovascular Health Research Unit, School of Medicine, University of Washington, Seattle, Washington, USA.
  • Kuo JZ; Department of Ophthalmology, University of Mississippi Medical Center, School of Medicine, University of Mississippi, Jackson, Mississippi, USA.
  • Li X; Department of Ophthalmology, University of Mississippi Medical Center, School of Medicine, University of Mississippi, Jackson, Mississippi, USA.
  • Chen YI; Department of Ophthalmology, University of Mississippi Medical Center, School of Medicine, University of Mississippi, Jackson, Mississippi, USA.
  • Rotter JI; Department of Ophthalmology, University of Mississippi Medical Center, School of Medicine, University of Mississippi, Jackson, Mississippi, USA.
  • Klein R; Clinical and Medical Affairs, CardioDx Inc., Redwood City, California, USA.
  • Klein B; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California, USA.
  • Wong TY; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California, USA.
  • Morris AD; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California, USA.
  • Doney ASF; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California, USA.
  • Colhoun HM; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California, USA.
  • Price AL; Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California, USA.
  • Burdon KP; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California, USA.
  • Groop PH; Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
  • Sandholm N; Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
  • Grassi MA; Singapore Eye Research Institute, Singapore National Eye Centre, Yong Loo Lin School of Medicine, National University of Singapore, Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore.
  • Sobrin L; The Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
  • Palmer CNA; Medical Research Institute, Ninewells Hospital and School of Medicine, University of Dundee, Dundee, UK.
Acta Ophthalmol ; 96(7): e811-e819, 2018 Nov.
Article em En | MEDLINE | ID: mdl-30178632
ABSTRACT

PURPOSE:

Diabetic retinopathy is the most common eye complication in patients with diabetes. The purpose of this study is to identify genetic factors contributing to severe diabetic retinopathy.

METHODS:

A genome-wide association approach was applied. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. Significant Single Nucleotide Polymorphisms (SNPs) were taken forward for meta-analysis using multiple Caucasian cohorts.

RESULTS:

Five hundred and sixty cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a p value of 4.05 × 10-9 . Two nearby SNPs, rs10765219 and rs11018670 also showed promising p values (p values = 7.41 × 10-8 and 1.23 × 10-8 , respectively). In the meta-analysis using multiple Caucasian cohorts (excluding GoDARTS), rs10765219 and rs11018670 showed associations for diabetic retinopathy (p = 0.003 and 0.007, respectively), while the p value of rs3913535 was not significant (p = 0.429).

CONCLUSION:

This genome-wide association study of severe diabetic retinopathy suggests new evidence for the involvement of the NOX4 gene.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Polimorfismo de Nucleotídeo Único / Diabetes Mellitus Tipo 2 / Retinopatia Diabética / NADPH Oxidase 4 Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged País como assunto: Europa Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
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Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Polimorfismo de Nucleotídeo Único / Diabetes Mellitus Tipo 2 / Retinopatia Diabética / NADPH Oxidase 4 Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged País como assunto: Europa Idioma: En Ano de publicação: 2018 Tipo de documento: Article