Brinkley Tina E, Leng Xiaoyan, Nicklas Barbara J, Kritchevsky Stephen B, Ding Jingzhong, Kitzman Dalane W, Hundley W Gregory
Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
Metabolism. 2017 May;70:98-106. doi: 10.1016/j.metabol.2017.02.008. Epub 2017 Feb 10.
Low levels of the soluble receptor for advanced glycation endproducts (sRAGE) have been implicated in a number of chronic diseases. Previous studies indicate that sRAGE levels are ~30% lower in Blacks compared to Whites. However, the reasons for these differences are unclear.
We aimed to identify predictors of circulating sRAGE biomarkers among Black and White adults at high cardiac risk.
Serum levels of total sRAGE, endogenous secretory RAGE (esRAGE), carboxymethyl-lysine (CML, a major RAGE ligand), and their ratios were measured in 99 Blacks and 454 Whites.
Blacks had a more adverse cardiovascular risk profile, as well as lower median levels of total sRAGE (972 vs. 1564pg/ml) and esRAGE (474 vs. 710pg/ml) compared to Whites (p<0.0001). In addition, the proportion of esRAGE was higher in Blacks (47% vs. 44%, p=0.02), as were the CML/total sRAGE (0.89 vs. 0.56ng/pg) and CML/esRAGE (1.72 vs. 1.20ng/pg) ratios (p<0.0001). Racial differences persisted after adjustment for key covariates including age, gender, tobacco use, comorbidities, BMI, blood pressure, glucose, insulin, triglycerides, C-reactive protein, and renal function (p<0.05). Race alone accounted for nearly half of the variability in total sRAGE levels (10.6%; model explained 23.9%). In stratified analyses, gender and heart rate were independently associated with total sRAGE and esRAGE in Whites, while CML and C-reactive protein were associated with total sRAGE in Blacks.
We identified several independent predictors of sRAGE biomarkers. Notably, Black race was associated with an adverse AGE/RAGE profile, including lower sRAGE and higher CML/sRAGE ratios.
晚期糖基化终产物可溶性受体（sRAGE）水平降低与多种慢性疾病有关。先前的研究表明，与白人相比，黑人的sRAGE水平低约30%。然而，这些差异的原因尚不清楚。
我们旨在确定高心脏疾病风险的黑人和白人成年人循环sRAGE生物标志物的预测因素。
测量了99名黑人及454名白人的血清总sRAGE、内源性分泌型RAGE（esRAGE）、羧甲基赖氨酸（CML，一种主要的RAGE配体）水平及其比值。
与白人相比，黑人具有更不利的心血管疾病风险特征，总sRAGE（972 vs. 1564pg/ml）和esRAGE（474 vs. 710pg/ml）的中位数水平更低（p<0.0001）。此外，黑人中esRAGE的比例更高（47% vs. 44%，p=0.02），CML/总sRAGE（0.89 vs. 0.56ng/pg）和CML/esRAGE（1.72 vs. 1.20ng/pg）比值也是如此（p<0.0001）。在对包括年龄、性别、吸烟、合并症、体重指数、血压、血糖、胰岛素、甘油三酯、C反应蛋白和肾功能等关键协变量进行调整后，种族差异仍然存在（p<0.05）。仅种族因素就占总sRAGE水平变异性的近一半（10.6%；模型解释率为23.9%）。在分层分析中，性别和心率与白人的总sRAGE和esRAGE独立相关，而CML和C反应蛋白与黑人的总sRAGE相关。
我们确定了sRAGE生物标志物的几个独立预测因素。值得注意的是，黑人种族与不良的糖基化终产物/受体晚期糖基化终产物（AGE/RAGE）特征相关，包括较低的sRAGE和较高的CML/sRAGE比值。
