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

doi:10.2337/db15-1484

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

Medicine

Research output: Contribution to journal › Article › peer-review

7 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 HbA_1c (P = 1.7 × 10^-8). rs7533564 was associated with mean HbA_1c 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 language	English (US)
Pages (from-to)	2060-2071
Number of pages	12
Journal	Diabetes
Volume	65
Issue number	7
DOIs	https://doi.org/10.2337/db15-1484
State	Published - Jul 1 2016

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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10.2337/db15-1484

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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

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

@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 = "Publisher Copyright: {\textcopyright} 2016 by the American Diabetes Association.",

year = "2016",

month = jul,

day = "1",

doi = "10.2337/db15-1484",

language = "English (US)",

volume = "65",

pages = "2060--2071",

journal = "Diabetes",

issn = "0012-1797",

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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.

AB - 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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SN - 0012-1797

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JO - Diabetes

JF - Diabetes

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ER -

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

Abstract

ASJC Scopus subject areas

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