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

Research output: Contribution to journalArticle

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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 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

Fingerprint

Type 1 Diabetes Mellitus
Diabetes Complications
Fluorescence
Skin
Proteins
Meta-Analysis
Epidemiology
Glyoxal
Advanced Glycosylation End Products
Acetyltransferases
Genetic Loci
Chromosomes, Human, Pair 1
Diabetic Retinopathy
Type 2 Diabetes Mellitus
Epidemiologic Studies
Collagen
Biopsy

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., ... 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

New locus for skin intrinsic fluorescence in type 1 diabetes also associated with blood and skin glycated proteins. / Roshandel, Delnaz; Klein, Ronald; Klein, Barbara E K; Wolffenbuttel, Bruce H R; 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 J.; Hosseini, S. Mohsen; Hiraki, Linda T.; Maynard, John; Sell, David R.; Monnier, Vincent M.; Cleary, Patricia A.; Braffett, Barbara H.; Paterson, Andrew D.

In: Diabetes, Vol. 65, No. 7, 01.07.2016, p. 2060-2071.

Research output: Contribution to journalArticle

Roshandel, D, Klein, R, Klein, BEK, Wolffenbuttel, BHR, Van Der Klauw, MM, Van Vliet-Ostaptchouk, JV, Atzmon, G, Ben-Avraham, D, Crandall, JP, Barzilai, N, Bull, SB, Canty, AJ, Hosseini, SM, Hiraki, LT, Maynard, J, Sell, DR, Monnier, VM, Cleary, PA, Braffett, BH & Paterson, AD 2016, 'New locus for skin intrinsic fluorescence in type 1 diabetes also associated with blood and skin glycated proteins', Diabetes, vol. 65, no. 7, pp. 2060-2071. https://doi.org/10.2337/db15-1484
Roshandel D, Klein R, Klein BEK, Wolffenbuttel BHR, Van Der Klauw MM, Van Vliet-Ostaptchouk JV et al. New locus for skin intrinsic fluorescence in type 1 diabetes also associated with blood and skin glycated proteins. Diabetes. 2016 Jul 1;65(7):2060-2071. https://doi.org/10.2337/db15-1484
Roshandel, Delnaz ; Klein, Ronald ; Klein, Barbara E K ; Wolffenbuttel, Bruce H R ; 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 J. ; Hosseini, S. Mohsen ; Hiraki, Linda T. ; Maynard, John ; Sell, David R. ; Monnier, Vincent M. ; Cleary, Patricia A. ; Braffett, Barbara H. ; Paterson, Andrew D. / New locus for skin intrinsic fluorescence in type 1 diabetes also associated with blood and skin glycated proteins. In: Diabetes. 2016 ; Vol. 65, No. 7. pp. 2060-2071.
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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 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.",
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T1 - New locus for skin intrinsic fluorescence in type 1 diabetes also associated with blood and skin glycated proteins

AU - Roshandel, Delnaz

AU - Klein, Ronald

AU - Klein, Barbara E K

AU - Wolffenbuttel, Bruce H R

AU - Van Der Klauw, Melanie M.

AU - Van Vliet-Ostaptchouk, Jana V.

AU - Atzmon, Gil

AU - Ben-Avraham, Danny

AU - Crandall, Jill P.

AU - Barzilai, Nir

AU - Bull, Shelley B.

AU - Canty, Angelo J.

AU - Hosseini, S. Mohsen

AU - Hiraki, Linda T.

AU - Maynard, John

AU - Sell, David R.

AU - Monnier, Vincent M.

AU - Cleary, Patricia A.

AU - Braffett, Barbara H.

AU - Paterson, Andrew D.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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.

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