Dataset Information

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.

ABSTRACT: 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.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.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.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.

SUBMITTER: Kaditis AG

PROVIDER: S-EPMC3940266 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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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.

Kaditis Athanasios G AG Gozal David D Khalyfa Abdelnaby A Kheirandish-Gozal Leila L Capdevila Oscar Sans OS Gourgoulianis Konstantinos K Alexopoulos Emmanouel I EI Chaidas Konstantinos K Bhattacharjee Rakesh R Kim Jinkwan J Rodopoulou Paraskevi P Zintzaras Elias E

Sleep medicine 20131204 2

<h4>Background</h4>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.<h4>Methods</h4>The genetic r ...[more]

PMID: 24380782

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Project description:Excessive daytime sleepiness (EDS) is a symptom of obstructive sleep apnea (OSA) that resolves under treatment with continuous positive airway pressure (CPAP). In some patients, sleepiness persists despite CPAP treatment. We retrospectively analyzed data on subjective residual EDS, assessed as an Epworth Sleepiness Scale score (ESS) >10, in patients from the European Sleep Apnea Database (n = 4,853, mean age ± SD 54.8 ± 11.8 years, 26.1% females), at baseline and at the first visit (median follow-up: 5 months, interquartile range 3-13). An ESS > 10 occurred in 56% of patients at baseline and in 28.2% of patients at follow-up. Residual EDS was analyzed in 2,190 patients (age: 55.1 ± 12.0 years, 26.1% females) with sleep monitoring data (median follow-up: 3 months, interquartile range 1-15). Sleep studies during CPAP use were obtained in 58% of these patients; EDS was reported by 47.2% of patients at baseline and by 30.3% at follow-up. Residual OSA, defined as an apnea-hypopnea index >10/h, and insufficient CPAP adherence, defined as nightly use <4 h, occurred with similar frequency in patients with and without EDS at follow-up. Prevalence of residual EDS was highest (40%) in patients with a first follow-up visit at 0-3 months, then it was 13-19% in patients with a first follow-up visit after 4 months to 2 years. The change in ESS (n = 2,190) was weakly correlated with CPAP use (R2 = 0.023, p < 0.0001). Logistic regression showed that an ESS score >10 at the first follow-up visit was associated directly with ESS at baseline and inversely with duration of follow-up, and CPAP use (R2 of the model: 0.417). EDS showed heterogeneity in different European countries both at baseline and at the first follow-up visit, suggesting modulation by cultural and lifestyle factors. In conclusion, residual EDS in CPAP-treated OSA occurred in approximately one in four patients at follow-up; its prevalence was highest (40%) in the first 3 months of treatment and subsequently decreased. The finding of residual EDS in a significant percentage of optimally treated OSA patients suggests that wake-promoting agents may be useful, but their indication should be evaluated after at least 3 months of treatment.

Project description:Study objectivesChanges in lymphocyte phenotype and functionality have been described in adult patients with obstructive sleep apnea (OSA). We hypothesized that OSA is associated with T lymphocyte alterations in children, particularly in T regulatory lymphocytes (T regs), and aimed to characterize circulating T lymphocyte subsets in children with OSA.DesignCross-sectional.SettingKosair Children's Hospital (Louisville, KY, USA) and Comer Children's Hospital (Chicago, IL, USA).ParticipantsConsecutively recruited children being evaluated for habitual snoring.InterventionsN/A.Measurements and resultsOvernight polysomnography (PSG) was performed and a fasting blood sample was obtained from the patients. Flow cytometry was performed on peripheral blood mononuclear cells stained for CD3, CD4, CD8, CD25, FOXP3, interleukin-4 (IL-4), interferon-? (IFN-?), and IL-17. Patients were divided into three groups based on their PSG: controls (apnea-hypopnea indices [AHI] < 1/h total sleep time [TST]), mild OSA (1 ? AHI < 5/hTST), moderate-severe OSA (AHI ? 5/h TST). The percentage of CD4+ and T reg lymphocytes differed across groups. Children with moderate-severe OSA had significantly reduced T reg than control children (median [interquartile range] 4.8 [3.8-5.7% CD4+] versus 7.8 [7.0-9.2% CD4+]; P < 0.001). There were also significant differences in the percentage of T helper 1 (Th1) lymphocytes and in Th1:Th2 ratios between groups. Children with moderate-severe OSA had increased Th1 cells (P = 0.001) and Th1:Th2 ratios (P = 0.0026) compared with children with mild OSA and control children. Associations between AHI and T reg (P = 0.0003; r = -0.46), CD4+ lymphocytes (P = 0.0047; r = -0.37), and Th1:Th2 ratios (P = 0.0009; r = 0.43) emerged. In addition, the percentage of T reg was inversely correlated with Th1:Th2 ratios (P = 0.029; r = -0.29).ConclusionsPediatric OSA is associated with reduced T reg population and altered Th1:Th2 balance toward Th1 predominance, suggesting a shift to a proinflammatory state. The changes in lymphocytic phenotypes associated with OSA may contribute to the variance in systemic inflammation and downstream morbidities associated with this condition.

Dataset Information

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.

Publications

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.

Similar Datasets

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