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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.

SUBMITTER: Roshandel D

PROVIDER: S-EPMC4915582 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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New Locus for Skin Intrinsic Fluorescence in Type 1 Diabetes Also Associated With Blood and Skin Glycated Proteins.

Roshandel Delnaz D Klein Ronald R Klein Barbara E K BE Wolffenbuttel Bruce H R BH van der Klauw Melanie M MM van Vliet-Ostaptchouk Jana V JV Atzmon Gil G Ben-Avraham Danny D Crandall Jill P JP Barzilai Nir N Bull Shelley B SB Canty Angelo J AJ Hosseini S Mohsen SM Hiraki Linda T LT Maynard John J Sell David R DR Monnier Vincent M VM Cleary Patricia A PA Braffett Barbara H BH Paterson Andrew D AD

Diabetes 20160412 7

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 Wi ...[more]

PMID: 27207532

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Project description:BackgroundA variant (rs1495741) in the gene for the N-acetyltransferase 2 (NAT2) protein is associated with skin intrinsic fluorescence (SIF), a noninvasive measure of advanced glycation end products and other fluorophores in the skin. Because NAT2 is involved in caffeine metabolism, we aimed to determine whether caffeine consumption is associated with SIF and whether rs1495741 is associated with SIF independently of caffeine.Materials and methodsSIF was measured in 1,181 participants with type 1 diabetes from the Epidemiology of Diabetes Interventions and Complications study. Two measures of SIF were used: SIF1, using a 375-nm excitation light-emitting diode (LED), and SIF14 (456-nm LED). Food frequency questionnaires were used to estimate mean caffeine intake. To establish replication, we examined a second type 1 diabetes cohort.ResultsHigher caffeine intake was significantly associated with higher SIF1(LED 375 nm[0.6, 0.2]) (P=2×10(-32)) and SIF14L(ED 456 nm[0.4, 0.8]) (P=7×10(-31)) and accounted for 4% of the variance in each after adjusting for covariates. When analyzed together, caffeine intake and rs1495741 both remained highly significantly associated with SIF1(LED 375 nm[0.6, 0.2]) and SIF14(LED 456 nm[0.4, 0.8]). Mean caffeinated coffee intake was also positively associated with SIF1(LED 375 nm[0.6, 0.2]) (P=9×10(-12)) and SIF14(LED 456 nm[0.4, 0.8]) (P=4×10(-12)), but no association was observed for decaffeinated coffee intake. Finally, caffeine was also positively associated with SIF1(LED 375 nm[0.6, 0.2]) and SIF14(LED 456 nm[0.4, 0.8]) (P<0.0001) in the replication cohort.ConclusionsCaffeine contributes to SIF. The effect of rs1495741 on SIF appears to be partially independent of caffeine consumption. Because SIF and coffee intake are each associated with cardiovascular disease, our findings suggest that accounting for coffee and/or caffeine intake may improve risk prediction models for SIF and cardiovascular disease in individuals with diabetes.

Dataset Information

New Locus for Skin Intrinsic Fluorescence in Type 1 Diabetes Also Associated With Blood and Skin Glycated Proteins.

Publications

New Locus for Skin Intrinsic Fluorescence in Type 1 Diabetes Also Associated With Blood and Skin Glycated Proteins.

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