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Sleep Med. 2014 Feb;15(2):228-35. doi: 10.1016/j.sleep.2013.08.795. Epub 2013 Dec 4.

Variants in C-reactive protein and IL-6 genes and susceptibility to obstructive sleep apnea in children: a candidate-gene association study in European American and Southeast European populations.

Author information

1
First Department of Pediatrics, University of Athens, School of Medicine and Aghia Sophia Children's Hospital, Athens, Greece. Electronic address: kaditia@hotmail.com.
2
Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL, United States; Division of Pediatric Sleep Medicine and Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY, United States.
3
Division of Pediatric Sleep Medicine and Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY, United States.
4
Sleep Disorders Laboratory, Larissa University Hospital, Larissa, Greece.
5
Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece.
6
Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece; Center for Clinical Evidence Synthesis, The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, United States.

Abstract

BACKGROUND:

Preliminary evidence indicates that variants of the C-reactive protein (CRP) and IL-6 genes might be associated with the presence of obstructive sleep apnea (OSA) in childhood. Thus a candidate-gene association study was conducted to investigate the association of four variants of the CRP gene (1444C/T, -717T/C, 1861C/T, and 1919A/T) and two variants of the IL-6 gene (-174G/C and 597G/A) with OSA in a cohort of European American and Greek children.

METHODS:

The genetic risk effects were estimated based on the odds ratio (OR) of the allele contrast and the generalized odds ratio (ORG), which is a model-free approach. The mode of inheritance was assessed using the degree of dominance index. The impact of haplotypes was also examined.

RESULTS:

In the American population, the allele contrast and the model-free approach produced significant ORs for the CRP 1444C/T variant (OR, 3.82 [95% confidence interval {CI}, 1.91-7.63] and ORG, 4.37 [95% CI, 1.96-9.76]), respectively, and the mode of inheritance was recessiveness of allele T. Significance was also shown for the CRP 1919A/T variant (OR, 2.45 [95% CI, 1.23-4.85] and ORG, 2.76 [95% CI, 1.26-6.03]) with the mode of inheritance being nondominance of allele T. For the IL-6-174G/C variant, there was an indication of recessiveness of allele C. Finally, the IL-6-174C/IL-6 597A haplotype was associated with OSA. In the Greek population, no association was detected for any variant or haplotype.

CONCLUSIONS:

Genetic variation in the IL-6/CRP pathway was associated with increased risk for OSA in European American children and may account for the higher CRP levels in the context of pediatric OSA compared to Greek children.

KEYWORDS:

C-reactive protein; Genetic association; Inflammation; Interleukin-6; Obstructive sleep apnea; Obstructive sleep-disordered breathing

PMID:
24380782
PMCID:
PMC3940266
DOI:
10.1016/j.sleep.2013.08.795
[Indexed for MEDLINE]
Free PMC Article
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