Macrophage migration inhibitory factor gene polymorphisms and plasma levels in children with obstructive sleep apnea

Pediatr Pulmonol. 2012 Oct;47(10):1001-11. doi: 10.1002/ppul.22560. Epub 2012 Mar 26.

Abstract

Introduction: Obstructive sleep apnea (OSA) is associated with increased risk for cardiovascular and metabolic dysfunction in both adults and children. In adults with OSA, serum levels of macrophage migration inhibitory factor (MIF) are elevated. Therefore, we assessed plasma MIF levels and MIF allelic variant frequencies in children with and without OSA (NOSA).

Methods: A total of 614 consecutive children ages 5-8 years were recruited. Children were divided into those with OSA and NOSA based on the apnea-hypopnea index (AHI). In addition to lipid profile, hsCRP, and fasting insulin and glucose levels, plasma MIF levels were assayed using ELISA, and 28 single nucleotide polymorphisms (SNPs) covering the region were genotyped. Linkage disequilibrium and haplotype blocks were analyzed using Haploview version 4.2 software.

Results: Morning plasma MIF levels were increased in children with OSA. Of the 28 SNPs tested, the frequency of rs10433310 minor allele was significantly decreased in OSA. This SNP was also associated with reduced fasting insulin and hsCRP levels in OSA. The minor allele frequency of all other 27 SNPs was similar in OSA and NOSA groups.

Conclusions: Childhood OSA is associated with higher plasma MIF, hsCRP, and fasting insulin levels that promote cardiometabolic risk, and the MIF gene SNP rs10433310 may account for some of the variance in such risk.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Blood Glucose / physiology
  • C-Reactive Protein / analysis
  • Child
  • Fasting / physiology
  • Female
  • Gene Frequency
  • Haplotypes
  • Humans
  • Insulin / blood
  • Intramolecular Oxidoreductases / blood*
  • Intramolecular Oxidoreductases / genetics*
  • Linkage Disequilibrium
  • Lipids / blood
  • Macrophage Migration-Inhibitory Factors / blood*
  • Macrophage Migration-Inhibitory Factors / genetics*
  • Male
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Polysomnography
  • Sleep Apnea, Obstructive / blood*

Substances

  • Blood Glucose
  • Insulin
  • Lipids
  • Macrophage Migration-Inhibitory Factors
  • C-Reactive Protein
  • Intramolecular Oxidoreductases
  • MIF protein, human