| Candidate gene association study for diabetic retinopathy in persons with type 2 diabetes: the Candidate gene Association Resource (CARe). | |
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MedLine Citation:
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PMID: 21873659 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: To investigate whether variants in cardiovascular candidate genes, some of which have been previously associated with type 2 diabetes (T2D), diabetic retinopathy (DR), and diabetic nephropathy (DN), are associated with DR in the Candidate gene Association Resource (CARe). METHODS: Persons with T2D who were enrolled in the study (n = 2691) had fundus photography and genotyping of single nucleotide polymorphisms (SNPs) in 2000 candidate genes. Two case definitions were investigated: Early Treatment Diabetic Retinopathy Study (ETDRS) grades ≥ 14 and ≥ 30. The χ² analyses for each CARe cohort were combined by Cochran-Mantel-Haenszel (CMH) pooling of odds ratios (ORs) and corrected for multiple hypothesis testing. Logistic regression was performed with adjustment for other DR risk factors. Results from replication in independent cohorts were analyzed with CMH meta-analysis methods. RESULTS: Among 39 genes previously associated with DR, DN, or T2D, three SNPs in P-selectin (SELP) were associated with DR. The strongest association was to rs6128 (OR = 0.43, P = 0.0001, after Bonferroni correction). These associations remained significant after adjustment for DR risk factors. Among other genes examined, several variants were associated with DR with significant P values, including rs6856425 tagging α-l-iduronidase (IDUA) (P = 2.1 × 10(-5), after Bonferroni correction). However, replication in independent cohorts did not reveal study-wide significant effects. The P values after replication were 0.55 and 0.10 for rs6128 and rs6856425, respectively. CONCLUSIONS: Genes associated with DN, T2D, and vascular diseases do not appear to be consistently associated with DR. A few genetic variants associated with DR, particularly those in SELP and near IDUA, should be investigated in additional DR cohorts. |
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Authors:
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Lucia Sobrin; Todd Green; Xueling Sim; Richard A Jensen; E Shyong Tai; Wan Ting Tay; Jie Jin Wang; Paul Mitchell; Niina Sandholm; Yiyuan Liu; Kustaa Hietala; Sudha K Iyengar; ; Matthew Brooks; Monika Buraczynska; Natalie Van Zuydam; Albert V Smith; Vilmundur Gudnason; Alex S F Doney; Andrew D Morris; Graham P Leese; Colin N A Palmer; ; Anand Swaroop; Herman A Taylor; James G Wilson; Alan Penman; Ching J Chen; Per-Henrik Groop; Seang-Mei Saw; Tin Aung; Barbara E Klein; Jerome I Rotter; David S Siscovick; Mary Frances Cotch; Ronald Klein; Mark J Daly; Tien Y Wong |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-09-29 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 52 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-30 Completed Date: 2011-12-13 Revised Date: 2012-03-01 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 7593-602 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA. lucia_sobrin@meei.harvard.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cardiovascular Diseases
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genetics* Diabetes Mellitus, Type 2 / genetics* Diabetic Nephropathies / genetics Diabetic Retinopathy / genetics* Genetic Predisposition to Disease* Genome-Wide Association Study Genotype Humans Iduronidase / genetics Odds Ratio P-Selectin / genetics Polymorphism, Single Nucleotide Risk Factors |
| Grant Support | |
ID/Acronym/Agency:
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K12-EY16335/EY/NEI NIH HHS; N01-HC-65226/HC/NHLBI NIH HHS; UL1 RR 025758/RR/NCRR NIH HHS; Z01 EY000401-06/EY/NEI NIH HHS; Z01 EY000401-07/EY/NEI NIH HHS; Z01 EY000403-06/EY/NEI NIH HHS; Z01 EY000403-07/EY/NEI NIH HHS; Z01 EY000425-04/EY/NEI NIH HHS; Z99 EY999999/EY/NEI NIH HHS; ZIA EY000401-08/EY/NEI NIH HHS; ZIA EY000401-09/EY/NEI NIH HHS; ZIA EY000401-10/EY/NEI NIH HHS; ZIA EY000403-08/EY/NEI NIH HHS; ZIA EY000403-09/EY/NEI NIH HHS; ZIA EY000403-10/EY/NEI NIH HHS; ZIA EY000425-06/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/P-Selectin; EC 3.2.1.76/Iduronidase |
| Investigator | |
Investigator/Affiliation:
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S K Iyengar / ; R C Elston / ; K A B Goddard / ; J M Olson / ; R P Igo / ; S Ialacci / ; C Fondran / ; J Fondran / ; A Horvath / ; G Jun / ; K Kramp / ; S R E Quade / ; M Slaughter / ; E Zaletel / ; J R Sedor / ; J Schelling / ; A Sehgal / ; A Pickens / ; L Humbert / ; L Getz-Fradley / ; S Adler / ; H E Collins-Schramm / ; E Ipp / ; H Li / ; M Pahl / ; M F Seldin / ; J LaPage / ; B Walker / ; C Garcia / ; J Gonzalez / ; L Ingram-Drake / ; M Klag / ; R Parekh / ; L Kao / ; L Mead / ; T Whitehead / ; J Chester / ; W C Knowler / ; R L Hanson / ; R G Nelson / ; A Malhotra / ; L Jones / ; R Juan / ; R Lovelace / ; C Luethe / ; L M Phillips / ; J Sewemaenewa / ; I Sili / ; B Waseta / ; M F Saad / ; S B Nicholas / ; X Guo / ; J Rotter / ; K Taylor / ; M Budgett / ; F Hariri / ; P Zager / ; V Shah / ; M Scavini / ; A Bobelu / ; H Abboud / ; N Arar / ; R Duggirala / ; B S Kasinath / ; R Plaetke / ; M Stern / ; C Jenkinson / ; C Goyes / ; V Sartorio / ; T Abboud / ; L Hernandez / ; B I Freedman / ; D W Bowden / ; S C Satko / ; S S Rich / ; S Warren / ; S Viverette / ; G Brooks / ; R Young / ; M Spainhour / ; C Winkler / ; M W Smith / ; M Thompson / ; R Hanson / ; B Kessing / ; R Danis / ; M Davis / ; J P Briggs / ; P L Kimmel / ; R Rasooly / ; E Y Chew / ; D Warnock / ; R Chakraborty / ; G M Dunston / ; S J O'Brien / ; R Spielman / ; Peter Donnelly / ; Ines Barroso / ; Jenefer M Blackwell / ; Elvira Bramon / ; Matthew A Brown / ; Juan P Casas / ; Aiden Corvin / ; Panos Deloukas / ; Audrey Duncanson / ; Janusz Jankowski / ; Hugh S Markus / ; Christopher G Mathew / ; Colin N A Palmer / ; Robert Plomin / ; Anna Rautanen / ; Stephen J Sawcer / ; Richard C Trembath / ; Ananth C Viswanathan / ; Nicholas W Wood / ; Chris C A Spencer / ; Gavin Band / ; Céline Bellenguez / ; Colin Freeman / ; Garrett Hellenthal / ; Eleni Giannoulatou / ; Matti Pirinen / ; Richard Pearson / ; Amy Strange / ; Zhan Su / ; Damjan Vukcevic / ; Peter Donnelly / ; Cordelia Langford / ; Sarah E Hunt / ; Sarah Edkins / ; Rhian Gwilliam / ; Hannah Blackburn / ; Suzannah J Bumpstead / ; Serge Dronov / ; Matthew Gillman / ; Emma Gray / ; Naomi Hammond / ; Alagurevathi Jayakumar / ; Owen T McCann / ; Jennifer Liddle / ; Simon C Potter / ; Radhi Ravindrarajah / ; Michelle Ricketts / ; Matthew Waller / ; Paul Weston / ; Sara Widaa / ; Pamela Whittaker / ; Ines Barroso / ; Panos Deloukas / ; Christopher G Mathew / ; Jenefer M Blackwell / ; Matthew A Brown / ; Aiden Corvin / ; Mark I McCarthy / ; Chris C A Spencer / |
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