A novel potential biomarker for metabolic syndrome in Chinese adults: Circulating protein disulfide isomerase family A, member 4

PLoS One. 2017 Jun 26;12(6):e0179963. doi: 10.1371/journal.pone.0179963. eCollection 2017.

Abstract

Background/objectives: Protein disulfide isomerase (PDI) family members are specific endoplasmic reticulum proteins that are involved in the pathogenesis of numerous diseases including neurodegenerative diseases, cancer and obesity. However, the metabolic effects of PDIA4 remain unclear in humans. The aims of this study were to investigate the associations of serum PDIA4 with the metabolic syndrome (MetS) and its components in Chinese adults.

Subjects/methods: A total of 669 adults (399 men and 270 women) were recruited. Serum PDIA4 concentrations and biochemical variables were recorded. Insulin sensitivity and β-cell function were examined by homeostasis model assessment. MetS was defined based on the modified National Cholesterol Education Program Adult Treatment Panel III criteria for Asia Pacific.

Results: The participants with MetS had significantly higher serum PDIA4 levels than those without MetS (P<0.001). After adjustments, the individuals with the highest PDIA4 tertile were associated with a higher risk of MetS than those with the lowest tertile (OR = 4.83, 95% CI: 2.71-8.60). The concentration of PDIA4 showed a stepwise increase with the components of MetS (P<0.001 for trend). The individuals with the highest PDIA4 tertile were significantly associated with waist circumference (OR = 2.41, 95% CI 1.34-4.32), blood pressure (OR = 2.71, 95% CI 1.57-4.67), fasting glucose concentration (OR = 3.17, 95% CI 1.80-5.57), and serum triglycerides (OR = 4.12, 95% CI 2.30-7.37) than those with the lowest tertile. At cutoff point of 15.24 ng/ml, the diagnostic sensitivity and specificity of PDIA4 for the metabolic syndrome were 67 and 72%, respectively, in male patients and 60 and 78%, respectively, in female patients. Finally, the result showed that PDIA4 had a significantly higher area under the curve compared with blood pressure to detect MetS using receiver operating characteristic analysis.

Conclusions: Serum PDIA4 concentrations are closely associated to MetS and its components in Chinese adults.

MeSH terms

  • Adult
  • Asian People
  • Biomarkers / blood
  • Case-Control Studies
  • Cross-Sectional Studies
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum Stress
  • Female
  • Humans
  • Male
  • Metabolic Syndrome / blood*
  • Metabolic Syndrome / enzymology*
  • Metabolic Syndrome / etiology
  • Middle Aged
  • Protein Disulfide-Isomerases / blood*
  • Risk Factors
  • Taiwan

Substances

  • Biomarkers
  • PDIA4 protein, human
  • Protein Disulfide-Isomerases

Grants and funding

This work was supported by research grants from the National Science Council (MOST 104-2314-B-016-026, MOST 104-2314-B-016-053, MOST 105-2314-B-016-040-MY3, MOST 105-2314-B-016-030-MY2), National Defense Medical Center (MAB-104-82), and Tri-Service General Hospital (TSGH-C105-005-S03, TSGH-C105-005-S04, TSGH-C106-006-S01, TSGH-C106-006-S02, TSGH-C106-007-S01, TSGH-C105-120, TSGH-C105-183, TSGH-C105-184, TSGH-C105-185), Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.