New Locus for Skin Intrinsic Fluorescence in Type 1 Diabetes Also Associated With Blood and Skin Glycated Proteins.
New Locus for Skin Intrinsic Fluorescence in Type 1 Diabetes Also Associated With Blood and Skin Glycated Proteins.
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DOI：
10.2337/db15-1484
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发表时间：
2016-07
期刊：
影响因子：
7.7
通讯作者：
Paterson AD
中科院分区：
文献类型：
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作者：
Roshandel D;Klein R;Klein BE;Wolffenbuttel BH;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;DCCT/EDIC Research Group;Paterson AD
皮肤荧光 (SF) 可无创地测量皮肤中的晚期糖基化终末产物 (AGE)，是糖尿病并发症的风险指标。 N-乙酰转移酶 2 (NAT2) 是唯一已知影响 SF 的位点。我们的目的是通过对全基因组关联研究 (N = 1,359) 的荟萃分析来确定影响 1 型糖尿病 (T1D) SF 的其他遗传位点，包括糖尿病控制和并发症试验/糖尿病干预和并发症流行病学 (DCCT/EDIC) 和威斯康星州糖尿病视网膜病变流行病学研究 (WESDR)。 1 号染色体上的一个位点 rs7533564 (P = 1.9 × 10−9) 与 SCOUT DS 测量的皮肤固有荧光（激发 375 nm，发射 435–655 nm）相关，在调整时间加权 HbA1c 后仍然显着（P = 1.7 × 10−8）。 rs7533564 与荟萃分析中的平均 HbA1c (P = 0.0225)、平均糖化白蛋白 (P = 0.0029) 和乙二醛氢咪唑酮 (P = 0.049)（DCCT 中皮肤活检胶原蛋白中测量的 AGE）相关。 rs7533564 与 DCCT/EDIC 中的糖尿病并发症或非糖尿病受试者（非糖尿病 [ND]）中的 SF 无关（N = 8,721）。总之，我们在 T1D 受试者中发现了一个与 SF 相关的新基因座，该基因座在 ND 受试者中没有表现出类似的效果，表明存在糖尿病特异性效应。需要在 2 型糖尿病中研究这种关联。
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.