Candidate Gene Association Study for Diabetic Retinopathy in Persons with Type 2 Diabetes: The Candidate Gene Association Resource (CARe)

Lucia Sobrin, Todd Green, Xueling Sim, Richard A. Jensen, E. Shyong Tai, Wan Ting Tay, Jie Jin Wang, Paul Mitchell, Niina Sandholm, Yiyuan Liu, Kustaa Hietala, Sudha K. Iyengar, Matthew Brooks, Monika Buraczynska, Natalie Van Zuydam, Albert V. Smith, Vilmundur Gudnason, Alex S. F. Doney, Andrew D. Morris, Graham P. LeeseColin N. A. Palmer, Anand Swaroop, Herman A. Taylor, James G. Wilson, Alan Penman, Ching J. Chen, Per-Henrik Groop, Seang-Mei Saw, Tin Aung, Barbara E. Klein, Jerome I. Rotter, David S. Siscovick, Mary Frances Cotch, Ronald Klein, Mark J. Daly, Tien Y. Wong, Wellcome Trust Case Control Consor, Family Invest Nephropathy Diabet-E

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    Abstract

    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 chi(2) 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 alpha-Liduronidase (IDUA) (P = 2.1 X 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. (Invest Ophthalmol Vis Sci. 2011;52:7593-7602) DOI:10.1167/iovs.11-7510

    Original languageEnglish
    Pages (from-to)7593-7602
    Number of pages10
    JournalInvestigative Ophthalmology & Visual Science
    Volume52
    Issue number10
    DOIs
    Publication statusPublished - Sep 2011

    Keywords

    • GENOME-WIDE ASSOCIATION
    • CORONARY-ARTERY-DISEASE
    • COMMON VARIANTS
    • RISK-FACTORS
    • ERYTHROPOIETIN GENE
    • LINKAGE ANALYSES
    • BLOOD-PRESSURE
    • UNITED-STATES
    • FTO GENE
    • COMPLICATIONS

    Cite this

    Sobrin, L., Green, T., Sim, X., Jensen, R. A., Tai, E. S., Tay, W. T., Wang, J. J., Mitchell, P., Sandholm, N., Liu, Y., Hietala, K., Iyengar, S. K., Brooks, M., Buraczynska, M., Van Zuydam, N., Smith, A. V., Gudnason, V., Doney, A. S. F., Morris, A. D., ... Wellcome Trust Case Control Consor, Family Invest Nephropathy Diabet-E (2011). Candidate Gene Association Study for Diabetic Retinopathy in Persons with Type 2 Diabetes: The Candidate Gene Association Resource (CARe). Investigative Ophthalmology & Visual Science, 52(10), 7593-7602. https://doi.org/10.1167/iovs.11-7510