Racial differences in circulating levels of the soluble receptor for advanced glycation endproducts in middle-aged and older adults

Metabolism. 2017 May:70:98-106. doi: 10.1016/j.metabol.2017.02.008. Epub 2017 Feb 10.


Background: 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.

Purpose: We aimed to identify predictors of circulating sRAGE biomarkers among Black and White adults at high cardiac risk.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Advanced glycation endproducts; Carboxymethyl-lysine; Endogenous secretory RAGE; Race; Soluble RAGE.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Black People
  • C-Reactive Protein / analysis
  • Female
  • Heart Rate
  • Humans
  • Lysine / analogs & derivatives
  • Lysine / blood
  • Male
  • Middle Aged
  • Racial Groups
  • Receptor for Advanced Glycation End Products / blood*
  • Sex Factors
  • White People


  • Receptor for Advanced Glycation End Products
  • esRAGE protein, human
  • sRAGE protein, human
  • N(6)-carboxymethyllysine
  • C-Reactive Protein
  • Lysine