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.
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.
Authors: Ryo Kawasaki; Ning Cheung; F M Amirul Islam; Ronald Klein; Barbara E K Klein; Mary Frances Cotch; A Richey Sharrett; Daniel O'Leary; Tien Y Wong Journal: Ophthalmology Date: 2010-12-18 Impact factor: 12.079
Authors: Kiran Musunuru; Guillaume Lettre; Taylor Young; Deborah N Farlow; James P Pirruccello; Kenechi G Ejebe; Brendan J Keating; Qiong Yang; Ming-Huei Chen; Nina Lapchyk; Andrew Crenshaw; Liuda Ziaugra; Anthony Rachupka; Emelia J Benjamin; L Adrienne Cupples; Myriam Fornage; Ervin R Fox; Susan R Heckbert; Joel N Hirschhorn; Christopher Newton-Cheh; Marcia M Nizzari; Dina N Paltoo; George J Papanicolaou; Sanjay R Patel; Bruce M Psaty; Daniel J Rader; Susan Redline; Stephen S Rich; Jerome I Rotter; Herman A Taylor; Russell P Tracy; Ramachandran S Vasan; James G Wilson; Sekar Kathiresan; Richard R Fabsitz; Eric Boerwinkle; Stacey B Gabriel Journal: Circ Cardiovasc Genet Date: 2010-04-17
Authors: Carol Yim-Lui Cheung; Tien Yin Wong; Ecosse L Lamoureux; Charumathi Sabanayagam; Jialiang Li; Jeanette Lee; E Shyong Tai Journal: Am J Epidemiol Date: 2009-12-11 Impact factor: 4.897
Authors: Zongzhong Tong; Zhenglin Yang; Shrena Patel; Haoyu Chen; Daniel Gibbs; Xian Yang; Vincent S Hau; Yuuki Kaminoh; Jennifer Harmon; Erik Pearson; Jeanette Buehler; Yuhong Chen; Baifeng Yu; Nicholas H Tinkham; Norman A Zabriskie; Jiexi Zeng; Ling Luo; Jennifer K Sun; Manvi Prakash; Rola N Hamam; Stephen Tonna; Ryan Constantine; Cecinio C Ronquillo; SriniVas Sadda; Robert L Avery; John M Brand; Nyall London; Alfred L Anduze; George L King; Paul S Bernstein; Scott Watkins; Lynn B Jorde; Dean Y Li; Lloyd Paul Aiello; Martin R Pollak; Kang Zhang Journal: Proc Natl Acad Sci U S A Date: 2008-05-05 Impact factor: 11.205
Authors: Richa Saxena; Benjamin F Voight; Valeriya Lyssenko; Noël P Burtt; Paul I W de Bakker; Hong Chen; Jeffrey J Roix; Sekar Kathiresan; Joel N Hirschhorn; Mark J Daly; Thomas E Hughes; Leif Groop; David Altshuler; Peter Almgren; Jose C Florez; Joanne Meyer; Kristin Ardlie; Kristina Bengtsson Boström; Bo Isomaa; Guillaume Lettre; Ulf Lindblad; Helen N Lyon; Olle Melander; Christopher Newton-Cheh; Peter Nilsson; Marju Orho-Melander; Lennart Råstam; Elizabeth K Speliotes; Marja-Riitta Taskinen; Tiinamaija Tuomi; Candace Guiducci; Anna Berglund; Joyce Carlson; Lauren Gianniny; Rachel Hackett; Liselotte Hall; Johan Holmkvist; Esa Laurila; Marketa Sjögren; Maria Sterner; Aarti Surti; Margareta Svensson; Malin Svensson; Ryan Tewhey; Brendan Blumenstiel; Melissa Parkin; Matthew Defelice; Rachel Barry; Wendy Brodeur; Jody Camarata; Nancy Chia; Mary Fava; John Gibbons; Bob Handsaker; Claire Healy; Kieu Nguyen; Casey Gates; Carrie Sougnez; Diane Gage; Marcia Nizzari; Stacey B Gabriel; Gung-Wei Chirn; Qicheng Ma; Hemang Parikh; Delwood Richardson; Darrell Ricke; Shaun Purcell Journal: Science Date: 2007-04-26 Impact factor: 47.728