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Macrophage migration inhibitory factor gene polymorphisms and plasma levels in children with obstructive sleep apnea
Abdelnaby Khalyfa1, Leila Kheirandish-Gozal, Oscar Sans Capdevila
1Department of Pediatrics, Comer Children's Hospital, The University of Chicago, Chicago, IL 60637, USA.
Insights
Childhood obstructive sleep apnea (OSA) is linked to higher macrophage migration inhibitory factor (MIF) and cardiometabolic risk. A specific MIF gene variant (rs10433310) may influence this risk in children with OSA.
Area of Science:
- Pediatric Endocrinology
- Sleep Medicine
- Genetics
Background:
- Obstructive sleep apnea (OSA) in children is a growing concern, linked to cardiovascular and metabolic issues.
- Elevated macrophage migration inhibitory factor (MIF) is observed in adult OSA patients.
- Investigating MIF in pediatric OSA is crucial for understanding associated health risks.
Purpose of the Study:
- To evaluate plasma MIF levels in children with and without OSA.
- To determine the frequency of MIF gene variants in pediatric OSA.
- To explore the association between MIF, its genetic variants, and cardiometabolic risk factors in children.
Main Methods:
- Recruited 614 children aged 5-8 years, categorized into OSA and non-OSA (NOSA) groups based on the apnea-hypopnea index (AHI).
- Assayed plasma MIF levels using ELISA and genotyped 28 single nucleotide polymorphisms (SNPs) in the MIF gene region.
- Analyzed lipid profiles, hsCRP, fasting insulin, and glucose levels.
Main Results:
- Children with OSA exhibited increased morning plasma MIF levels.
- The minor allele frequency of MIF SNP rs10433310 was significantly lower in the OSA group.
- This SNP was associated with reduced fasting insulin and hsCRP levels in children with OSA.
Conclusions:
- Childhood OSA is associated with elevated plasma MIF, hsCRP, and fasting insulin, contributing to cardiometabolic risk.
- The MIF gene SNP rs10433310 may partially explain the variability in cardiometabolic risk associated with pediatric OSA.
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.
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