Glycoprotein 130 polymorphism predicts soluble glycoprotein 130 levels

Interleukin-6 (IL-6) is a key cytokine in inflammatory diseases. It exerts its biological function via binding to a homodimer of its signal transducer glycoprotein 130 (gp130). Soluble gp130 (sgp130) is the natural inhibitor of IL-6 trans-signalling. The aim of this study was to test a possible influence of the gp130 genotype on sgp130 serum levels.

In two separate populations, subjects were genotyped for the gp130 polymorphism G148C. Sgp130, IL-6 and soluble interleukin-6 receptor (sIL-6R) levels were measured. The OSLO population consisted of 546 male subjects at high risk for CAD. The VIENNA population consisted of 299 male subjects with angiographically proven CAD.

In the OSLO population, 124 (22.7%) subjects were hetero- or homozygote for the rare C allele. Individuals carrying the polymorphism had significantly higher levels of sgp130. In a multivariate linear regression model this association remained significant (adjusted p=0.001). In the VIENNA population, 48 (16.1%) subjects were hetero- or homozygote for the rare C allele. Consistent with the former study, sgp130 levels were significantly higher in carriers of the polymorphism compared to wildtype carriers (adjusted p=0.038). In the VIENNA population, sgp130 levels were significantly higher in diabetic patients. In the OSLO population, sgp130 was higher in patients with increased body mass index and in smokers (p<0.05).

Sgp130 serum levels are significantly higher in subjects carrying the gp130 polymorphism G148C compared to wildtype carriers. This finding proposes a possible genetical influence on sgp130 levels which may alter individual coping mechanisms in inflammatory diseases.