An investigation of serum concentration of apoM as a potential MODY3 marker using a novel ELISA
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Published on: June 14, 2018
C Cervin1, O Axler, J Holmkvist
1Department of Clinical Sciences, Diabetes & Endocrinology, Clinical Research Centre, Malmö University Hospital, Lund University, Malmö, Sweden.
Objective:
To investigate the fitness of serum apolipoprotein M (apoM) concentration as a marker for maturity-onset diabetes of the young 3 (MODY3).
Study Design And Subjects:
This study consisted of two parts. A family study included 71 carriers of the P291fsinsC mutation in hepatocyte nuclear factor-1alpha (HNF-1alpha) from the Finnish Botnia study, 53 of whom were diabetic, and 75 matched family controls. A second, case-control study included 24 MODY3 patients, 17 healthy MODY3 mutation carriers, 11 MODY1 patients, 18 type 2 diabetes patients and 19 healthy control individuals. Subjects in the case-control study were recruited from the Botnia study or the Clinic of Endocrinology, Malmö University Hospital. Serum apoM levels were measured using a novel ELISA based on two monoclonal apoM antibodies.
Results:
In the family study, mean serum apoM was 10% lower in female carriers of the P291fsinsC mutation compared to the family controls (P = 0.0058), a difference which remained significant after adjustment for diabetes status. There was no observed difference between groups for men. In the case-control study, no significant difference in apoM concentration was observed between MODY3 and type 2 diabetes patients, neither before nor after adjustment for total cholesterol.
Conclusions:
Female carriers of the P291fsinsC mutation in HNF-1alpha displayed slightly lower apoM serum levels. This difference is too small for apoM to be reliably employed as a biomarker for HNF-1alpha mutation status.
Insights
Serum apolipoprotein M (apoM) levels were slightly lower in women with the HNF-1alpha mutation. This finding suggests apoM is not a reliable biomarker for detecting maturity-onset diabetes of the young 3 (MODY3).
Area of Science:
- Endocrinology
- Genetics
- Metabolic Diseases
Background:
- Maturity-onset diabetes of the young type 3 (MODY3) is a monogenic form of diabetes caused by mutations in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene.
- Apolipoprotein M (apoM) is a protein found in human serum that has been investigated for its role in lipid metabolism and diabetes.
Purpose of the Study:
- To evaluate the utility of serum apolipoprotein M (apoM) concentration as a diagnostic marker for maturity-onset diabetes of the young 3 (MODY3).
- To assess the relationship between HNF-1alpha gene mutations and serum apoM levels.
Main Methods:
- A family study involving carriers of the P291fsinsC HNF-1alpha mutation and matched controls.
- A case-control study comparing MODY3 patients, healthy mutation carriers, MODY1 patients, type 2 diabetes patients, and healthy controls.
- Serum apoM levels were quantified using a novel enzyme-linked immunosorbent assay (ELISA).
Main Results:
- Female carriers of the P291fsinsC HNF-1alpha mutation exhibited a statistically significant, albeit small, decrease in serum apoM levels compared to controls, even after adjusting for diabetes status.
- No significant difference in serum apoM levels was observed between men carrying the mutation and controls.
- Serum apoM concentrations did not differ significantly between MODY3 patients and type 2 diabetes patients, irrespective of total cholesterol levels.
Conclusions:
- Female carriers of the P291fsinsC HNF-1alpha mutation have slightly reduced serum apoM levels.
- The observed difference in apoM levels is not substantial enough for apoM to serve as a reliable biomarker for identifying HNF-1alpha mutation status or diagnosing MODY3.
