The CD14-260 C → T promoter polymorphism co-segregates with the tumor necrosis factor-α (TNF-α)-308 G → A polymorphism and is associated with the interleukin-1β (IL-1β) synthesis capacity of human leukocytes

Genetic variations contribute to the interindividual variance in the cytokine response to endotoxin. The gene of tumor necrosis factor-α (TNF-α) carries a polymorphism at position -308 of the promoter, consisting of a G/A exchange. To further elucidate the inherited mechanisms influencing cytokine levels, healthy human blood donors were studied. Genotyping for the TNF-α -308 and the CD14 -260 C/T promoter polymorphisms was carried out by real-time polymerase chain reaction assay using specific fluorescence-labelled hybridisation probes. A human whole blood assay was used to study the leukocyte TNF-α and IL-1β synthesis capacity upon endotoxin stimulation. We found a linkage disequilibrium between the TNF-α -308 G/A and the CD14 -260 C/T polymorphisms (p = 0.043). The CD14 -260 polymorphism was associated with IL-1β levels (p = 0.033) and higher values were found in C homozygotes. No association was found between the CD14 -260 genotypes or the TNF-α -308 - CD14 -260 genotypes and the TNF-α response.