New locus for skin intrinsic fluorescence in type 1 diabetes also associated with blood and skin glycated proteins

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

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6 Scopus citations

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 genomewide 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.

Original languageEnglish (US)
Pages (from-to)2060-2071
Number of pages12
JournalDiabetes
Volume65
Issue number7
DOIs
StatePublished - Jul 1 2016

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Roshandel, D., Klein, R., Klein, B. E. K., Wolffenbuttel, B. H. R., Van Der Klauw, M. M., Van Vliet-Ostaptchouk, J. V., Atzmon, G., Ben-Avraham, D., Crandall, J. P., Barzilai, N., Bull, S. B., Canty, A. J., Hosseini, S. M., Hiraki, L. T., Maynard, J., Sell, D. R., Monnier, V. M., Cleary, P. A., Braffett, B. H., & Paterson, A. D. (2016). New locus for skin intrinsic fluorescence in type 1 diabetes also associated with blood and skin glycated proteins. Diabetes, 65(7), 2060-2071. https://doi.org/10.2337/db15-1484