Plasma concentrations of afamin are associated with the prevalence and development of metabolic syndrome

Circ Cardiovasc Genet. 2014 Dec;7(6):822-9. doi: 10.1161/CIRCGENETICS.113.000654. Epub 2014 Aug 31.

Abstract

Background: Afamin is a human plasma vitamin E-binding glycoprotein primarily expressed in the liver and secreted into the bloodstream. Because little is known about (patho)-physiological functions of afamin, we decided to identify phenotypes associated with afamin by investigating transgenic mice overexpressing the human afamin gene and performing large-scale human epidemiological studies.

Methods and results: Transgenic mice overexpressing afamin revealed increased body weight and serum concentrations of lipids and glucose. We applied a random-effects meta-analysis using age- and sex-adjusted baseline and follow-up investigations in the population-based Bruneck (n=826), Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR; n=1499), and KOoperative Gesundheitsforschung in der Region Augsburg (KORA) F4 studies (n=3060). Mean afamin concentrations were 62.5±15.3, 66.2±14.3, and 70.6±17.2 mg/L in Bruneck, SAPHIR, and KORA F4, respectively. Per 10 mg/L increment in afamin measured at baseline, the number of metabolic syndrome components increased by 19% (incidence rate ratio=1.19; 95% confidence interval [CI], 1.16-1.21; P=5.62×10(-64)). With the same afamin increment used at baseline, we observed an 8% gain in metabolic syndrome components between baseline and follow-up (incidence rate ratio=1.08; 95% CI, 1.06-1.10; P=8.87×10(-16)). Afamin concentrations at baseline were highly significantly related to all individual metabolic syndrome components at baseline and at follow-up. This observation was most pronounced for elevated waist circumference (odds ratio, 1.79; 95% CI, 1.54-2.09; P=4.15×10(-14) at baseline and odds ratio, 1.46; 95% CI, 1.31-1.63; P=2.84×10(-11) for change during follow-up) and for elevated fasting glucose concentrations (odds ratio, 1.46; 95% CI, 1.40-1.52; P=1.87×10(-69) and odds ratio, 1.46; 95% CI, 1.24-1.71; P=5.13×10(-6), respectively).

Conclusions: This study in transgenic mice and >5000 participants in epidemiological studies shows that afamin is strongly associated with the prevalence and development of metabolic syndrome and all its components.

Keywords: afamin protein, human; epidemiology; glucose; lipoproteins; metabolic syndrome X; metabolism; obesity.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Blood Glucose / analysis
  • Body Weight
  • Carrier Proteins / blood*
  • Databases, Factual
  • Female
  • Follow-Up Studies
  • Glycoproteins / blood*
  • Humans
  • Logistic Models
  • Male
  • Metabolic Syndrome / epidemiology*
  • Metabolic Syndrome / pathology
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Prevalence
  • Serum Albumin
  • Serum Albumin, Human

Substances

  • AFM protein, human
  • Blood Glucose
  • Carrier Proteins
  • Glycoproteins
  • Serum Albumin
  • Serum Albumin, Human