TY - JOUR
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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U2 - 10.2337/db15-1484
DO - 10.2337/db15-1484
M3 - Article
C2 - 27207532
AN - SCOPUS:84975883796
VL - 65
SP - 2060
EP - 2071
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 7
ER -