@article{da5dac5558d04b01aada65f643aeed19,
title = "New locus for skin intrinsic fluorescence in type 1 diabetes also associated with blood and skin glycated proteins",
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.",
author = "Delnaz Roshandel and Ronald Klein and Klein, {Barbara E.K.} and Wolffenbuttel, {Bruce H.R.} and {Van Der Klauw}, {Melanie M.} and {Van Vliet-Ostaptchouk}, {Jana V.} and Gil Atzmon and Danny Ben-Avraham and Crandall, {Jill P.} and Nir Barzilai and Bull, {Shelley B.} and Canty, {Angelo J.} and Hosseini, {S. Mohsen} and Hiraki, {Linda T.} and John Maynard and Sell, {David R.} and Monnier, {Vincent M.} and Cleary, {Patricia A.} and Braffett, {Barbara H.} and Paterson, {Andrew D.}",
note = "Funding Information: Industry contributors have provided free or discounted supplies or equipment to support participants' adherence to the study: Abbott Diabetes Care (Alameda, CA), Animas (Westchester, PA), Bayer Diabetes Care (North America Headquarters, Tarrytown, NY), Becton Dickinson (Franklin Lakes, NJ), Eli Lilly (Indianapolis, IN), Extend Nutrition (St. Louis, MO), Insulet Corporation (Bedford, MA), LifeScan (Milpitas, CA), Medtronic Diabetes (Minneapolis, MN), Nipro Home Diagnostics (Ft. Lauderdale, FL), Nova Diabetes Care (Billerica, MA), Omron (Shelton, CT), Perrigo Diabetes Care (Allegan, MI), Roche Diabetes Care (Indianapolis, IN), and Sanofi (Bridgewater, NJ). The DCCT/EDIC has been supported by cooperative agreement grants (1982-1993 and 2012-2017) and contracts (1982-2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) (current grant nos. U01-DK-094176 and U01-DK-094157) and by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006-present), Bethesda, MD. The skin biopsy ancillary substudy in DCCT/EDIC was funded by the NIDDK (DK-79432 to D.R.S.) and the JDRF International (grant no. 17-2010-318 to V.M.M.). The WESDR was supported by grant R01-EY016379 from the National Eye Institute, National Institutes of Health (NIH), and an unrestricted grant from Research to Prevent Blindness, New York, NY. The LifeLines Cohort Study is supported by the Netherlands Organization for Scientific Research (grant 175.010.2007.006); Economic Structure Enhancing Fund of the Dutch government; Ministry of Economic Affairs, Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; Northern Netherlands Provinces Alliance; Province of Groningen; University Medical Center Groningen; Dutch Kidney Foundation; and Dutch Diabetes Research Foundation. Participation in this work was in part also supported by the National Consortium for Healthy Ageing and the BioSHaRE-EU consortium (KP7, project reference 261433). LifeLines (BRIF4568) is engaged in a Bioresource research impact factor policy pilot study, details of which can be found at www.bioshare.eu/content/bioresource-impact-factor. LonGenity is supported by the NIH (P01-AG027734 to N.B.), Glenn Foundation for the Biology of Aging, Nathan Shock Center (P30AG038072), Einstein Institute for Clinical and Translational Research (Clinical and Translational Science Awards grant 8UL1 TR000086 from the National Center for Advancing Translational Sciences), Diabetes Research Center (NIH-5P60-DK-20541), and NIH (RO11R01AG042188 to G.A.). Industry contributors have had no role in the DCCT/EDIC study. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Eye Institute or the NIH.",
year = "2016",
month = jul,
day = "1",
doi = "10.2337/db15-1484",
language = "English (US)",
volume = "65",
pages = "2060--2071",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "7",
}