Genetic variants in interleukin-6 modified risk of obstructive sleep apnea syndrome

Abstract

Abstract. Obesity and inflammation are 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 phenotypically increase in patients with OSAS. This study aimed to investigate whether genetic variants in IL-6 confer susceptibility to OSAS. The study population consisted of 151 patients with OSAS and 75 healthy controls from Southeast China. Five haplotype-tagging single nucleotide polymorphisms (tSNPs) were selected across 21 kb of the IL-6 locus using Haploview software V4.1. The tSNPs were amplified by polymerase chain reaction (PCR) and genotyped by restriction enzyme digestion followed by gel electrophoresis. Linkage disequilibrium (LD) and haplotype reconstruction were carried out by means of a SHEsis program. No distribution difference of any of the five tSNPs between OSAS patients and controls was observed. However, in nonobese individuals (n=117), the minor allele G (rs1800796) decreased risk of OSAS compared with the major allele C [odds ratio (OR), 0.48; 95% confidence interval (CI), 0.26-0.86; p=0.014], and the haplotype TG (rs1880242, rs1800796) conferred a significantly decreased risk of OSAS than single allele G (rs1800796) (OR, 0.39; 95% CI, p=0.003). Moreover, the severity of sleep-disordered breathing (measured by apnea hypopnea index) increased linearly in carriers of the C variant of IL-6 -572G/C polymorphism (14.3±5.1, 22.0±3.6 and 34.8±3.5 for GG, CG and CC, respectively; p=0.012). 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 is a potential strategy for detecting the risk of breathing disordered diseases in non-obese individuals.

The role inflammatory response genes in obstructive sleep apnea syndrome: a review

“…According to Zhang et al, a polymorphism found in the promoter region of IL6 gene (−G174C) affects its gene expression. A similar role in the metabolism of the adipose tissue was also attributed to TNF-α where its levels also depend on the presence of a polymorphism (-G308A) in the promoter region of TNFA [58]. The presence of the A allele can double the expression of this gene, leading to a higher production of TNF-α.…”

“…The presence of the A allele can double the expression of this gene, leading to a higher production of TNF-α. Thus, it is possible to infer that the influence of the lipid metabolism and the energetic expenditure is linked to the concentration of these cytokines, which might contribute to weight gain in OSAS [42], being also a common risk factor for obesity and metabolic disturbances, especially insulin resistance [58].…”

5-HTR2A and IL-6 polymorphisms and obstructive sleep apnea-hypopnea syndrome

“…However, the minor allele 'G' (rs1800796) decreased the risk of OSAS in non-obese subjects, compared with the major allele 'C' (OR, 0.48; 95% CI, 0.26-0.86; P=0.014). We believe it is primarily attributed to the different definition for overweight or obese patients (BMI ≥25 vs. ≥27 kg/m 2 ), and in addition, subgroup analysis was not conducted according to the severity of disease in the Zhang et al (24) study.…”

“…These differences were ascribed to the distinct genetic background and the different living environments of the Chinese population compared with other ethnicities. Zhang et al (24) identified that no distribution difference in the IL-6 gene was observed between OSAS patients and controls in the Chinese Han population. However, the minor allele 'G' (rs1800796) decreased the risk of OSAS in non-obese subjects, compared with the major allele 'C' (OR, 0.48; 95% CI, 0.26-0.86; P=0.014).…”

Interleukin-6 -634C>G polymorphism in hypertensive patients with and without left ventricular hypertrophy

“…IL-6 is a pleiotropic cytokine of 23.7 kDa secreted by many cells of the immune system, cardiovascular components and adipose tissue, and functions as a mediator of inflammatory response with both pro-and anti-inflammatory properties (8). Circulating levels of IL-6 differ greatly between individuals (8,9), due to genetic and environmental factors (10).…”