Athanasios G Kaditis1, David Gozal2, Abdelnaby Khalyfa2, Leila Kheirandish-Gozal2, Oscar Sans Capdevila3, Konstantinos Gourgoulianis4, Emmanouel I Alexopoulos4, Konstantinos Chaidas4, Rakesh Bhattacharjee2, Jinkwan Kim2, Paraskevi Rodopoulou5, Elias Zintzaras6. 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.
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.
Authors: Athanasios G Kaditis; Emmanouel I Alexopoulos; Efthimia Kalampouka; Eleni Kostadima; Anastasios Germenis; Elias Zintzaras; Konstantinos Gourgoulianis Journal: Am J Respir Crit Care Med Date: 2004-11-19 Impact factor: 21.405
Authors: S Redline; P V Tishler; T D Tosteson; J Williamson; K Kump; I Browner; V Ferrette; P Krejci Journal: Am J Respir Crit Care Med Date: 1995-03 Impact factor: 21.405
Authors: Dana C Crawford; Qian Yi; Joshua D Smith; Cynthia Shephard; Michelle Wong; Laura Witrak; Robert J Livingston; Mark J Rieder; Deborah A Nickerson Journal: Hum Genet Date: 2006-03-21 Impact factor: 4.132
Authors: L Kheirandish-Gozal; A Gileles-Hillel; M L Alonso-Álvarez; E Peris; R Bhattacharjee; J Terán-Santos; J Duran-Cantolla; D Gozal Journal: Int J Obes (Lond) Date: 2015-03-24 Impact factor: 5.095