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Candidate gene association study for diabetic retinopathy in persons with type 2 diabetes: the Candidate gene Association Resource (CARe).
Tuesday,2013-01-15 11:09 America/Los_Angeles — poolea2
| Title | Candidate gene association study for diabetic retinopathy in persons with type 2 diabetes: the Candidate gene Association Resource (CARe). |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Sobrin, L, Green, T, Sim, X, Jensen, RA, Tai, SE, Tay, WTing, Wang, JJin, Mitchell, P, Sandholm, N, Liu, Y, Hietala, K, Iyengar, SK, Brooks, M, Buraczynska, M, Van Zuydam, N, Smith, AV, Gudnason, V, Doney, ASF, Morris, AD, Leese, GP, Palmer, CNA, Swaroop, A, Taylor, HA, Wilson, JG, Penman, A, Chen, CJ, Groop, P-H, Saw, S-M, Aung, T, Klein, BE, Rotter, JI, Siscovick, DS, Cotch, MFrances, Klein, R, Daly, MJ, Wong, TY |
| Corporate/Institutional Authors | Family Investigation of Nephropathy and Diabetes-Eye Research Group,, Wellcome Trust Case Control Consortium 2, |
| Journal | Invest Ophthalmol Vis Sci |
| Volume | 52 |
| Issue | 10 |
| Pagination | 7593-602 |
| Date Published | 2011 Sep 29 |
| ISSN | 1552-5783 |
| Keywords | Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Diabetic Retinopathy, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Iduronidase, Odds Ratio, P-Selectin, Polymorphism, Single Nucleotide, Risk Factors |
| Abstract | <p><b>PURPOSE: </b>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).</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1167/iovs.11-7510 |
| Alternate Journal | Invest. Ophthalmol. Vis. Sci. |
| PubMed ID | 21873659 |
| PubMed Central ID | PMC3183981 |
| Grant List | ZIA EY000401-09 / / Intramural NIH HHS / United States ZIA EY000401-13 / / Intramural NIH HHS / United States Z99 EY999999 / / Intramural NIH HHS / United States ZIA EY000401-11 / / Intramural NIH HHS / United States ZIA EY000403-13 / / Intramural NIH HHS / United States ZIA EY000425-06 / / Intramural NIH HHS / United States ZIA EY000403-14 / / Intramural NIH HHS / United States K12 EY016335 / EY / NEI NIH HHS / United States ZIA EY000401-08 / / Intramural NIH HHS / United States ZIA EY000403-11 / / Intramural NIH HHS / United States K12-EY16335 / EY / NEI NIH HHS / United States ZIA EY000401-12 / / Intramural NIH HHS / United States ZIA EY000403-10 / / Intramural NIH HHS / United States ZIA EY000403-09 / / Intramural NIH HHS / United States Z01 EY000403-06 / / Intramural NIH HHS / United States 090532 / / Wellcome Trust / United Kingdom ZIA EY000403-08 / / Intramural NIH HHS / United States ZIA EY000401-15 / / Intramural NIH HHS / United States N01HC65226 / HL / NHLBI NIH HHS / United States Z01 EY000403-07 / / Intramural NIH HHS / United States Z01 EY000401-06 / / Intramural NIH HHS / United States UL1 RR025758 / RR / NCRR NIH HHS / United States UL1 RR 025758 / RR / NCRR NIH HHS / United States ZIA EY000403-15 / / Intramural NIH HHS / United States ZIA EY000401-14 / / Intramural NIH HHS / United States Z01 EY000401-07 / / Intramural NIH HHS / United States Z01 EY000425-04 / / Intramural NIH HHS / United States ZIA EY000401-10 / / Intramural NIH HHS / United States ZIA EY000403-12 / / Intramural NIH HHS / United States N01-HC-65226 / HC / NHLBI NIH HHS / United States |