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Invest Ophthalmol Vis Sci. 2011 Sep 29;52(10):7593-602. doi: 10.1167/iovs.11-7510.

Candidate gene association study for diabetic retinopathy in persons with type 2 diabetes: the Candidate gene Association Resource (CARe).

Collaborators (155)

Iyengar SK, Elston RC, Goddard KA, Olson JM, Igo RP, Ialacci S, Fondran C, Fondran J, Horvath A, Jun G, Kramp K, Quade SR, Slaughter M, Zaletel E, Sedor JR, Schelling J, Sehgal A, Pickens A, Humbert L, Getz-Fradley L, Adler S, Collins-Schramm HE, Ipp E, Li H, Pahl M, Seldin MF, LaPage J, Walker B, Garcia C, Gonzalez J, Ingram-Drake L, Klag M, Parekh R, Kao L, Mead L, Whitehead T, Chester J, Knowler WC, Hanson RL, Nelson RG, Malhotra A, Jones L, Juan R, Lovelace R, Luethe C, Phillips LM, Sewemaenewa J, Sili I, Waseta B, Saad MF, Nicholas SB, Guo X, Rotter J, Taylor K, Budgett M, Hariri F, Zager P, Shah V, Scavini M, Bobelu A, Abboud H, Arar N, Duggirala R, Kasinath BS, Plaetke R, Stern M, Jenkinson C, Goyes C, Sartorio V, Abboud T, Hernandez L, Freedman BI, Bowden DW, Satko SC, Rich SS, Warren S, Viverette S, Brooks G, Young R, Spainhour M, Winkler C, Smith MW, Thompson M, Hanson R, Kessing B, Danis R, Davis M, Briggs JP, Kimmel PL, Rasooly R, Chew EY, Warnock D, Chakraborty R, Dunston GM, O'Brien SJ, Spielman R, Donnelly P, Barroso I, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A, Deloukas P, Duncanson A, Jankowski J, Markus HS, Mathew CG, Palmer CN, Plomin R, Rautanen A, Sawcer SJ, Trembath RC, Viswanathan AC, Wood NW, Spencer CC, Band G, Bellenguez C, Freeman C, Hellenthal G, Giannoulatou E, Pirinen M, Pearson R, Strange A, Su Z, Vukcevic D, Donnelly P, Langford C, Hunt SE, Edkins S, Gwilliam R, Blackburn H, Bumpstead SJ, Dronov S, Gillman M, Gray E, Hammond N, Jayakumar A, McCann OT, Liddle J, Potter SC, Ravindrarajah R, Ricketts M, Waller M, Weston P, Widaa S, Whittaker P, Barroso I, Deloukas P, Mathew CG, Blackwell JM, Brown MA, Corvin A, McCarthy MI, Spencer CC.

Author information

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA.



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).


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.


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.


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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