Endocrine Abstracts

Matrix-GLA-protein (MGP) was repeatedly associated with inflammation markers during the last decade. It is expressed in leucocytes and is a regulator of immune response. Due to posttranslational modification, there are 4 forms. The form responsible for immunomodulation is still unknown. Since the predicted active form - carboxylated, phosphorylated MGP - is not directly associated with immunomodulation, we aimed to investigate the association of dp-ucMGP (dephosphorylated, uncarboxylated) with systemic inflammation parameters and diseases with a known inflammatory component. We analysed data from the BioPersMed cohort (n = 792, 55.8% females, mean age 58 +/- 9 years), a prospective cohort of asymptomatic subjects at cardiovascular risk. Dp-ucMGP was measured with IDS-iSYS InaKtif MGP Kit (Immunodiagnostic Systems Holdings PLC, UK). The tertiles ranged from 0 to 410 (1st), 411 to 515 (2nd) and 516 pmol/l to highest value (3rd). C-reactive protein (CRP), cystatin C and ferritin were measured via immunotubidimetry at a Roche Cobas c system (Roche Diagnostics, Vienna, Austria). CRP: values >5 mg/ml, cystatin C: values >0.95 mg/ml and Ferritin: values >140 ng/ml (females) or >360 ng/ml (males) were defined as increased. Sarcopenia was defined by appendicular skeletal muscle mass index. Appendicular skeletal muscle mass was determined by Lunar iDXA (GE Healthcare GmbH, Austria). We defined diabetes mellitus (DM) according to ADA criteria. The presence of non-alcoholic fatty liver disease (NAFLD) was determined based on medical records. Dp-ucMGP correlates significantly with CRP and cystatin C (Rho: 0.204, 0.348, respectively; P < 0.001 both) but not with ferritin. CRP, cystatin C and ferritin increase significantly (P < 0.001, P < 0.001, P = 0.028, respectively) per dp-ucMGP tertile. Furthermore, persons with increased CRP, cystatin C or ferritin show significantly increased dp-ucMGP levels (P = 0.002, P < 0.001, P = 0.048, respectively). Dp-ucMGP levels are significantly higher in DM patients (P < 0.001) (as CRP, cystatin C, ferritin, all P < 0.001) and in persons with NAFLD (P = 0.006) (as CRP and ferritin, both P < 0.001) and lower in sarcopenic individuals (P = 0.012) as CRP (P = 0.011) and ferritin (P = 0.049). MGP might not only be an interesting biomarker for the development of diseases via regulation of calcium homeostasis but also for the modulation of immune responses. Out of the MGP subforms dp-ucMGP could be a good candidate and needs further investigation.