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 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.affiliation: Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Delnaz
authors.initials: D
authors.lastname: Roshandel
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI.
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI.
authors.forename: Barbara E K
authors.initials: BE
authors.lastname: Klein
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Bruce H R
authors.initials: BH
authors.lastname: Wolffenbuttel
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Melanie M
authors.initials: MM
authors.lastname: van der Klauw
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Jana V
authors.initials: JV
authors.lastname: van Vliet-Ostaptchouk
authors.affiliation: Departments of Medicine and Genetics, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY Department of Natural Science, University of Haifa, Haifa, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Atzmon
authors.affiliation: Departments of Medicine and Genetics, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Danny
authors.initials: D
authors.lastname: Ben-Avraham
authors.affiliation: Departments of Medicine and Genetics, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Jill P
authors.initials: JP
authors.lastname: Crandall
authors.affiliation: Departments of Medicine and Genetics, Institute for Aging Research and the Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Shelley B
authors.initials: SB
authors.lastname: Bull
authors.affiliation: Department of Mathematics and Statistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Angelo J
authors.initials: AJ
authors.lastname: Canty
authors.affiliation: Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: S Mohsen
authors.initials: SM
authors.lastname: Hosseini
authors.affiliation: Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Linda T
authors.initials: LT
authors.lastname: Hiraki
authors.affiliation: VeraLight, Inc., Albuquerque, NM.
authors.forename: John
authors.initials: J
authors.lastname: Maynard
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH.
authors.forename: David R
authors.initials: DR
authors.lastname: Sell
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH Department of Biochemistry, Case Western Reserve University, Cleveland, OH.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Monnier
authors.affiliation: Biostatistics Center, George Washington University, Rockville, MD.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cleary
authors.affiliation: Biostatistics Center, George Washington University, Rockville, MD.
authors.forename: Barbara H
authors.initials: BH
authors.lastname: Braffett
authors.affiliation: Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada andrew.paterson@utoronto.ca.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
mesh_terms: D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D005453:Fluorescence; D005787:Gene Frequency; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012867:Skin / Q000000981:diagnostic imaging / Q000378:metabolism*