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DOI: 10.1055/s-2006-932919
IL-6 receptor polymorphism associated with impaired glucose metabolism
Objectives: IL-6 is a central mediator of inflammatory processes that was described to be elevated even before the onset of type 2 diabetes (T2DM). IL-6 exerts its biological function via its receptor or by binding to the soluble form of the IL-6 receptor (sIL-6R). In this way the effect of IL-6 is modified by sIL-6R. The amount of sIL-6R has been described associated with the D358A polymorphismus within the IL-6 receptor gene. Therefore, we investigated whether this polymorphism is associated with impaired glucose metabolism.
Methods: SNP analysis was restricted to the D358A polymorphism because of the functional data available and because of the tight linkage of all known polymorphisms within the IL-6 receptor gene. SNP detection was performed using TaqMan chemistry in 860 subjects of the cross-sectional MeSyBePo study cohort. Impaired glucose metabolism (IGM) was defined as known diabetes, impaired fasting glucose or an 2 hour OGTT value >140mg/dl. The results are indicated as mean±SD.
Results: 467 participants had normal glucose tolerance (NGT) and 393 participants had IGM (156 T2DM). The distribution of the DD, DA and AA genotypes were 27.8%, 43.7%, and 28.5%. Subjects carrying the A-allele did not differ in age or BMI (52.2±14.2 vs. 51.0±13.8 years and 28.6±6.1 vs. 28.7±6.7kg/m2). Furthermore, in the subgroup with NGT, HOMA-IR was not different in the A-allele carriers (2.0±1.5 vs. 2.2±2.0). Nevertheless, even after adjustment for sex, age, body-mass-index, waist-to-hip-ratio, and serum IL-6 the A-allele was significantly associated with IGM yielding a 1.34 fold increased probability for IGM (95% CI 1.07–1.68).
Conclusion: The D358A IL-6 receptor polymorphism was associated with impaired glucose metabolism in this german cohort. The mechanism might be an increased IL-6 effect in case of the A-allele due to increased sIL-6R levels. However, the impact of this polymorphism on glucose metabolism needs to be evaluated in further cohorts, especially, since the data so far available are conflicting.