TY - JOUR T1 - Candidate gene association study for diabetic retinopathy in persons with type 2 diabetes: the Candidate gene Association Resource (CARe). JF - Invest Ophthalmol Vis Sci Y1 - 2011 A1 - Sobrin, Lucia A1 - Green, Todd A1 - Sim, Xueling A1 - Jensen, Richard A A1 - Tai, E Shyong A1 - Tay, Wan Ting A1 - Wang, Jie Jin A1 - Mitchell, Paul A1 - Sandholm, Niina A1 - Liu, Yiyuan A1 - Hietala, Kustaa A1 - Iyengar, Sudha K A1 - Brooks, Matthew A1 - Buraczynska, Monika A1 - Van Zuydam, Natalie A1 - Smith, Albert V A1 - Gudnason, Vilmundur A1 - Doney, Alex S F A1 - Morris, Andrew D A1 - Leese, Graham P A1 - Palmer, Colin N A A1 - Swaroop, Anand A1 - Taylor, Herman A A1 - Wilson, James G A1 - Penman, Alan A1 - Chen, Ching J A1 - Groop, Per-Henrik A1 - Saw, Seang-Mei A1 - Aung, Tin A1 - Klein, Barbara E A1 - Rotter, Jerome I A1 - Siscovick, David S A1 - Cotch, Mary Frances A1 - Klein, Ronald A1 - Daly, Mark J A1 - Wong, Tien Y KW - Cardiovascular Diseases KW - Diabetes Mellitus, Type 2 KW - Diabetic Nephropathies KW - Diabetic Retinopathy KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - Genotype KW - Humans KW - Iduronidase KW - Odds Ratio KW - P-Selectin KW - Polymorphism, Single Nucleotide KW - Risk Factors AB -
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.
VL - 52 IS - 10 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21873659?dopt=Abstract ER -