04125nas a2200745 4500008004100000022001400041245014300055210006900198260001600267300001300283490000700296520189000303653002802193653003002221653002702251653002502278653003802303653003402341653001302375653001102388653001602399653001502415653001502430653003602445653001702481100001802498700001602516700001702532700002302549700001902572700001902591700001902610700001902629700002002648700001602668700002002684700002202704700002002726700002402746700002402770700002102794700002402815700002102839700002202860700002102882700002302903700001902926700002202945700002102967700001702988700001903005700002203024700001903046700001403065700002203079700002203101700002403123700002503147700001803172700001803190700001803208710007203226710004503298856003603343 2011 eng d a1552-578300aCandidate gene association study for diabetic retinopathy in persons with type 2 diabetes: the Candidate gene Association Resource (CARe).0 aCandidate gene association study for diabetic retinopathy in per c2011 Sep 29 a7593-6020 v523 a
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.
10aCardiovascular Diseases10aDiabetes Mellitus, Type 210aDiabetic Nephropathies10aDiabetic Retinopathy10aGenetic Predisposition to Disease10aGenome-Wide Association Study10aGenotype10aHumans10aIduronidase10aOdds Ratio10aP-Selectin10aPolymorphism, Single Nucleotide10aRisk Factors1 aSobrin, Lucia1 aGreen, Todd1 aSim, Xueling1 aJensen, Richard, A1 aTai, Shyong, E1 aTay, Wan, Ting1 aWang, Jie, Jin1 aMitchell, Paul1 aSandholm, Niina1 aLiu, Yiyuan1 aHietala, Kustaa1 aIyengar, Sudha, K1 aBrooks, Matthew1 aBuraczynska, Monika1 aVan Zuydam, Natalie1 aSmith, Albert, V1 aGudnason, Vilmundur1 aDoney, Alex, S F1 aMorris, Andrew, D1 aLeese, Graham, P1 aPalmer, Colin, N A1 aSwaroop, Anand1 aTaylor, Herman, A1 aWilson, James, G1 aPenman, Alan1 aChen, Ching, J1 aGroop, Per-Henrik1 aSaw, Seang-Mei1 aAung, Tin1 aKlein, Barbara, E1 aRotter, Jerome, I1 aSiscovick, David, S1 aCotch, Mary, Frances1 aKlein, Ronald1 aDaly, Mark, J1 aWong, Tien, Y1 aFamily Investigation of Nephropathy and Diabetes-Eye Research Group1 aWellcome Trust Case Control Consortium 2 uhttps://chs-nhlbi.org/node/1567