| Part 1 The Investigation of Serum Interleukin-6 in Patients with Obstructive Sleep Apnea SyndromeObjective To investigate the serum levels of Interleukin-6 (IL-6) in patients with obstructive sleep apnea syndrome( OSAS),and explore the relationship between the IL-6 and OSAS.Method 100 patients(88 males and 12 females) with OSAS diagnosed by polysomnography(PSG) were selected as patient group(AHI≥5/h).The patient group was classified into three subgroups according to the severity of apnea: mild OSAS group(5≤AHI≤20,n=25),moderate OSAS group(2040,n=58). 18 persons(14 males and 4 females )with snoring were chosen as control group (AHI<5/h).Except the severe group ,all patients and controls were matched for age and body mass index(BMI). Enzyme-linked immunosorbent assay was performed to determine the serum levels of IL-6 of groups mentioned above and to analyse differences between groups as well as correlations between IL-6 and sleep-breathing parameters in patients.Result 1.Compared with control subjects(0.9±0.3 pg/ml), serum IL-6 was significantly higher in OSAS patients(2.3±1.1 pg/ml ()p<0.05).2. There were significant differences of IL-6 among subgroups of the OSAS patients . The differences also existed between each subgroup and controls(p<0.05).The IL-6 averages of the three subgroups were 1.4±0.3 pg/ml in the mild group, 1.8±0.2 pg/ml in the moderate group and 2.9±1.1 pg/m in the severe group, respectively. And the average level of IL-6 of the severe subgroup was markedly higher than others. 3. The level of IL-6 has a positive correlation with AHI, oxygen desaturation index(ODI)and percentage of sleep time with SaO2 below 90% ( TRTSAO2<90% ) , respectively.(r=0.645, p<0.01;r=0.537, p <0.01;r=0.452, p<0.01),and a negative correlation with the average SaO2 and the lowest SaO2 .(r=-0.560, p <0.01;r=-0.538, p<0.001) in OSAS patients..Conclusion 1. Levels of IL-6 were elevated in patients with OSAS. 2. The elevated serum levels of IL-6 were proportional to the severity of OSAS which indicated that there existed inflammatory responses in the OSAS patients. 3. OSAS and obesity may both contribute to the highest IL-6 levels of the severe group.Part 2 Genetic Variants in Interleukin-6 Modified Risk of Obstructive Sleep Apnea SyndromeObjective Obesity and inflammation has been well known to correlate with the pathogenesis of obstructive sleep apnea syndrome (OSAS). Interleukin (IL-6), an important regulator of obesity and inflammation, was reported to increase phenotypically in patients with OSAS. This study aimed to investigate whether genetic variants in IL-6 could confer susceptibility to OSAS.Methods The study population consisted of 151 patients with OSAS and 75 healthy controls from the southeast of China. Five haplotype-tagging single nucleotide polymorphisms (tSNPs) were selected across 21 kb of the IL-6 locus using Haploview software V4.1.They were rs1404008,rs1880242,rs10499563,rs1800796 and rs2069837 .The tSNPs were amplified by polymerase chain reaction (PCR) and genotyped by restriction enzyme digestion followed by gelelectrophoresis. Linkage disequilibrium (LD) and haplotypes reconstruction were carried out by means of SHEsis program. Logistic regression was performed to assess odds ratios (OR) and 95% confidence intervals (CI), which were adjusted for gender, age and BMI.Result 1. No distribution difference of any of five tSNPs between OSAS patients and controls was observed. 2. In non-obese individuals (n = 117), the minor allele -572G decreased risk of OSAS compared with the major allele -572C [odds ratio (OR), 0.48; 95% confidence interval (95% CI), 0.26-0.86; p = 0.014], and the genotype -572(GG+CG) also decreased risk of OSAS compared with the the genotype -572CC(OR=0.38;95%CI,0.17-0.88,p=0.008 ). 3. The haplotype TG (rs1880242, rs1800796) carried by non-obese individuals conferred significantly more decreased risk of OSAS than other haplotypes (OR, 0.39; 95% CI, 0.20-0.74; p = 0.003). 4. The severity of sleep-disordered breathing (measured by AHI,times/h) increased linearly in carriers of the C variant of IL-6 -572G/C polymorphism in non-obese individuals (14.3±5.1, 22.0±3.6 and 34.8±3.5 for GG, CG and CC, respectively; p = 0.012).Conclusion The study indicated that genotype CC and allele C of -572G/C polymorphism of IL-6 gene in non-obese individuals could increase the risk of OSAS.Oppositely, genotype GG and allele G may have some protective effect to OSAS. Some haplotypes could play various roles in modifying the predisposition of OSAS in Chinese population.To the best of our knowledge, this is the first study to suggest that genetic variants in IL-6 could modify OSAS susceptibility. SNP genotyping of IL-6 gene could be a potential strategy to detect the risk of breathing disordered diseases in non-obese individuals. |
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