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

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 (OR_G), 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 OR_G, 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 OR_G, 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.