New Locus for Skin Intrinsic Fluorescence in Type 1 Diabetes Also Associated With Blood and Skin Glycated Proteins Academic Article uri icon

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abstract

  • Skin fluorescence (SF) noninvasively measures advanced glycation end products (AGEs) in the skin and is a risk indicator for diabetes complications. N-acetyltransferase 2 (NAT2) is the only known locus influencing SF. We aimed to identify additional genetic loci influencing SF in type 1 diabetes (T1D) through a meta-analysis of genome-wide association studies (N = 1,359) including Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) and Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). A locus on chromosome 1, rs7533564 (P = 1.9 × 10(-9)), was associated with skin intrinsic fluorescence measured by SCOUT DS (excitation 375 nm, emission 435-655 nm), which remained significant after adjustment for time-weighted HbA1c (P = 1.7 × 10(-8)). rs7533564 was associated with mean HbA1c in meta-analysis (P = 0.0225), mean glycated albumin (P = 0.0029), and glyoxal hydroimidazolones (P = 0.049), an AGE measured in skin biopsy collagen, in DCCT. rs7533564 was not associated with diabetes complications in DCCT/EDIC or with SF in subjects without diabetes (nondiabetic [ND]) (N = 8,721). In conclusion, we identified a new locus associated with SF in T1D subjects that did not show similar effect in ND subjects, suggesting a diabetes-specific effect. This association needs to be investigated in type 2 diabetes.

authors

  • Roshandel, Delnaz
  • Klein, Ronald
  • Klein, Barbara EK
  • Wolffenbuttel, Bruce HR
  • van der Klauw, Melanie M
  • van Vliet-Ostaptchouk, Jana V
  • Atzmon, Gil
  • Ben-Avraham, Danny
  • Crandall, Jill P
  • Barzilai, Nir
  • Bull, Shelley B
  • Canty, Angelo
  • Hosseini, S Mohsen
  • Hiraki, Linda T
  • Maynard, John
  • Sell, David R
  • Monnier, Vincent M
  • Cleary, Patricia A
  • Braffett, Barbara H
  • Paterson, Andrew D

publication date

  • July 2016