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Updated: Oct 23, 2025

Real-time Analyses of Retinol Transport by the Membrane Receptor of Plasma Retinol Binding Protein
Published on: January 28, 2013
Circulating retinol binding protein 4 levels in coronary artery disease: a systematic review and meta-analysis
Hengying Chen1,2, Jiaying Zhang3, Jiayu Lai3
1Injury Prevention Research Center, Shantou University Medical College, Shantou, China.
Insights
Retinol binding protein 4 (RBP4) levels in coronary artery disease (CAD) patients were comparable to controls, suggesting RBP4 may not be a significant risk factor. Further research with larger sample sizes is needed for definitive conclusions.
Area of Science:
- Cardiovascular Disease Research
- Biomarker Discovery
- Metabolic Health
Background:
- Retinol binding protein 4 (RBP4) is implicated in cardiovascular disease pathophysiology.
- Previous studies on RBP4 levels and coronary artery disease (CAD) have yielded inconsistent results.
- Understanding the role of RBP4 in CAD is crucial for developing effective diagnostic and therapeutic strategies.
Purpose of the Study:
- To conduct a meta-analysis evaluating the association between circulating RBP4 levels and CAD.
- To synthesize findings from observational studies to clarify the relationship between RBP4 and CAD.
- To provide a comprehensive overview of current evidence regarding RBP4 as a potential CAD biomarker.
Main Methods:
- A systematic meta-analysis of observational studies was performed.
- Literature search included PubMed, Web of Science, Embase, Google Scholar, and ClinicalTrials.gov up to July 12, 2021.
- Standard mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using various models (IVhet, random-effects, fixed-effects) based on heterogeneity (I²).
Main Results:
- The meta-analysis included 15 studies with 7111 participants.
- Overall, circulating RBP4 levels were comparable between CAD patients and controls (SMD: 0.25, 95% CI: -0.29-0.79) with high heterogeneity (I²: 96.00%).
- A significant association was observed under the random-effects model (SMD: 0.46, 95% CI: 0.17-0.75), but the 95% predictive interval included null values. Subgroup analysis showed a positive association in patients with complications (SMD: 1.34, 95% CI: 0.38-2.29).
Conclusions:
- Low-quality evidence suggests similar circulating RBP4 levels in CAD patients and controls.
- High inter-study heterogeneity complicates definitive conclusions regarding RBP4 as a CAD risk factor.
- Future research should focus on larger sample sizes and investigate different RBP4 subtypes to clarify its role in CAD.
Background:
Retinol binding protein 4 (RBP4) has been proposed to play a role in the pathophysiology of coronary artery disease (CAD), but previous findings on the association of RBP4 levels with CAD are inconsistent.
Methods:
A meta-analysis based on observational studies was conducted to evaluate the association between circulating RBP4 levels and CAD. Databases including PubMed, Web of Science, Embase, Google Scholar and ClinicalTrials.gov database were searched for eligible studies published up to 12 July 2021. Standard mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using the inverse variance heterogeneity (IVhet) and random-effects model for data with moderate and high heterogeneity (I2 > 30%) and data with low heterogeneity were analysed using a fixed-effects model (I2 ≤ 30%). Moreover, a bias-adjusted quality-effects model was generated, and the prediction interval was also calculated under the random-effects model.
Results:
Two nested case-control studies, one cohort study and twelve case-control studies with a total of 7111 participants were included. Circulating RBP4 levels in patients with CAD were comparable to those in the controls under the IVhet model (SMD: 0.25, 95% CI: - 0.29-0.79, I2: 96.00%). The quality-effects model produced consistent results. However, the association turned to be significant under the random-effect model (SMD: 0.46, 95% CI: 0.17-0.75, I2: 96.00%), whereas the 95% predictive interval (PI) included null values (95% PI: - 0.82-1.74). Subgroup analyses illustrated a positive relationship between CAD and RBP4 levels in patients with complications (SMD: 1.34, 95% CI: 0.38-2.29, I2: 96.00%). The meta-regression analysis revealed that the mean BMI of patients (P = 0.03) and complication status (P = 0.01) influenced the variation in SMD.
Conclusions:
There was low-quality evidence that patients with CAD exhibited similar circulating RBP4 levels compared with controls, and high inter-study heterogeneity was also observed. Thus, RBP4 might not be a potential risk factor for CAD. Comparisons among different subtypes of RBP4 with larger sample size are needed in the future.

