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  • Genetic analysis of advanced glycation end products in the DHS MIND study

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    AdamsPUB3153.pdf (337.9Kb)
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    Accepted Manuscript (AM)
    Author(s)
    Adams, Jeremy N
    Raffield, Laura M
    Martelle, Susan E
    Freedman, Barry I
    Langefeld, Carl D
    Carr, J Jeffrey
    Cox, Amanda J
    Bowden, Donald W
    Griffith University Author(s)
    Cox, Amanda J.
    Year published
    2016
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    Abstract
    Advanced glycation end-products (AGEs) are a diverse group of molecules produced by the non-enzymatic addition of glucose to proteins, lipids, and nucleic acids. AGE levels have been associated with hyperglycemia and diabetic complications, especially in animal models, but less clearly in human studies. We measured total serum AGEs using an enzyme linked immunosorbant assay (ELISA) in 506 subjects from 246 families in the Diabetes Heart Study (DHS)/DHS MIND Study (n = 399 type 2 diabetes (T2D)-affected). Single nucleotide polymorphisms (SNPs) in several candidate genes, including known AGE receptors, were tested for their ...
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    Advanced glycation end-products (AGEs) are a diverse group of molecules produced by the non-enzymatic addition of glucose to proteins, lipids, and nucleic acids. AGE levels have been associated with hyperglycemia and diabetic complications, especially in animal models, but less clearly in human studies. We measured total serum AGEs using an enzyme linked immunosorbant assay (ELISA) in 506 subjects from 246 families in the Diabetes Heart Study (DHS)/DHS MIND Study (n = 399 type 2 diabetes (T2D)-affected). Single nucleotide polymorphisms (SNPs) in several candidate genes, including known AGE receptors, were tested for their influence on circulating AGE levels. The genetic analysis was expanded to include an exploratory genome-wide association study (GWAS) and exome chip analysis of AGEs (≈ 440,000 SNPs). AGEs were found to be highly heritable (h2 = 0.628, p = 8.96 × 10–10). While no SNPs from candidate genes were significantly associated after Bonferroni correction, rs1035798 in the gene AGER was the most significantly associated (p = 0.007). Additionally, rs7198427, in MT1A, showed a nominally significant p-value (p = 0.0099). No SNPs from the GWAS or exome studies were identified after correction for multiple comparisons; however, rs17054480 in the PALLD2 gene on chromosome 4 showed the strongest association (p = 7.77 × 10− 7). Five SNPs at two loci (ISCA2/NPC2 and FBXO33) had p-values of less than 2.0 × 10− 5 and three additional SNPs (rs716326 in MACROD2, and rs6795197 and rs6765857 in ZBTB38) showed a nominal association with p-values of less than 1.0 × 10− 5.These findings provide a foundation for further investigation into the genetic component of circulating AGEs.
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    Journal Title
    Gene
    Volume
    584
    Issue
    2
    DOI
    https://doi.org/10.1016/j.gene.2016.02.029
    Copyright Statement
    © 2016 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
    Subject
    Genetics
    Genetics not elsewhere classified
    Zoology
    Medical microbiology
    Publication URI
    http://hdl.handle.net/10072/142887
    Collection
    • Journal articles

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