APOLIPOPROTEIN M

Sammanfattning: Apolipoprotein M (apoM) is composed of 188 amino acids and has an apparent molecular weight of 25 kDa. ApoM belongs to the lipocalin protein superfamily, and is found in all major lipoprotein classes, although the majority of apoM is found in high density lipoprotein, HDL. In apoM, the signal peptide is retained in the mature protein. ApoM with a cleavable signal peptide was constructed. In contrast to wild-type protein, the size of apoM with a cleaved signal peptide corresponded to free, unassociated apoM, strongly indicating that the signal peptide is necessary for the protein´s ability to associate with lipoproteins. To facilitate clinical studies, an ELISA for the measurement of apoM was developed and reference ranges established using samples from the NOBIDA biobank. Correlation studies of apoM with 26 common clinical chemical analytes was performed and a marked positive correlation was observed with plasma total cholesterol (r=0.52) and LDL and HDL cholesterol (r=0.43 and 0.36, respectively). To investigate whether apoM levels predict the risk for coronary disease, apoM was measured in samples from CHD and control subjects drawn from two prospective case-control studies, FINRISK ´92 and the Copenhagen City Heart Study (255 and 1865 individuals in total, respectively). In conditional logistic regression analyses, apoM was not a predictor of CHD events. Plasma apoM was investigated as a possible biomarker for MODY3 disease. Mean serum apoM was 5% lower in carriers of the P291fsinsC mutation of HNF-1a compared to family control subjects. The difference remained statistically significant after exclusion of diabetic individuals but is too small for apoM to be employed as a biomarker for HNF-1a mutation status. In a separate study, no significant difference in apoM concentration was observed between MODY3 and type 2 diabetic patients.