Cytokine gene polymorphisms in obstructive sleep apnoea/hypopnoea syndrome

Objective: The pro-inflammatory cytokines, TNF-alpha, IL-6, and IL-8 are elevated in obstructive sleep apnoea/hypopnoea syndrome (OSAHS). Cytokine gene interactions are complex and haplotype analysis may be more informative. We hypothesized that the effects of TNF-alpha in OSAHS might be due to linkage disequilibrium of the TNF-alpha (-308A) single nucleotide polymorphism (SNP) with other polymorphisms within the TNF-alpha gene, and that predisposition to elevated IL-6 and IL-8 levels in OSAHS might be attributable to pro-inflammatory IL-6 and IL-8 gene promoter polymorphisms.

Method: 173 subjects were classified as having definite OSAHS or not on the basis of apnoea-hypopnoea frequency, sex, age, and symptoms. Population controls comprised 192 random UK blood donors. Genotyping was undertaken for the TNF-alpha promoter polymorphisms (-1031, -863, -857, -238), two lymphotoxin-a polymorphisms (intron 1 and Thr60Asn), the pro-inflammatory IL-6 gene promoter polymorphism (-174), and IL-8 gene promoter polymorphisms (-251; -781).

Results: There was no significant difference between groups re: genotype/allelic frequency in the genes investigated. Association between disease status and the TNF-alpha alleles independently (TNF-103, TNF-803, TNF-857, TNF-238) with five haplotypes of TNF-alpha was not significant (p > 0.05). There was no difference in allelic or genotypic frequencies between obese and non-obese subjects with OSAHS. The TNF-alpha (-863A) allele alone, was significantly associated with obesity (OR 2.4; CI95% 1.1-5; p = 0.025).

Conclusion: Only the TNF-alpha (308A) SNP appears to be significantly associated with OSAHS. The impact of cytokine gene polymorphisms on phenotypic expression of inflammation in OSAHS is likely to be complex. (C) 2015 Published by Elsevier B.V.