Cytokine gene polymorphisms in obstructive sleep apnoea/hypopnoea syndrome

Objective: The pro-inflammatory cytokines, TNF-α, 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-α in OSAHS might be due to linkage disequilibrium of the TNF-α (-308A) single nucleotide polymorphism (SNP) with other polymorphisms within the TNF-α 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-α promoter polymorphisms (-1031, -863, -857, -238), two lymphotoxin-α 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-α alleles independently (TNF-103, TNF-803, TNF-857, TNF-238) with five haplotypes of TNF-α 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-α (-863A) allele alone, was significantly associated with obesity (OR 2.4; CI95% 1.1-5; p = 0.025).

Conclusion: Only the TNF-α (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.