Can complement factors 5 and 8 and transthyretin be used as biomarkers for MODY 1 (HNF4A-MODY) and MODY 3 (HNF1A-MODY)?
OBJECTIVE
Genetic testing is needed for the formal diagnosis of maturity-onset diabetes of the young (MODY), but this is not widely available. If any MODY biomarkers were known, these could possibly be used as an alternative. Hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha regulate transcription of genes encoding complement 5 (C5), complement 8 (C8) and transthyretin (TTR), suggesting that these could be potential biomarkers for the disease. We therefore set out to determine whether serum concentrations of C5, C8 and TTR can be used as biomarkers for patients with HNF4A-MODY and HNF1A-MODY.


METHODS
The serum concentrations of C5, C8 and TTR were analysed in patients with mutations in the HNF-1alpha (n=29) and HNF-4alpha (N=13) genes. Type 2 diabetic (n = 14) and healthy subjects (n = 20), matched for body mass index (BMI), served as diabetic and non-diabetic control groups, respectively.


RESULTS
Type 2 diabetic patients had markedly increased levels of C5 and C8 compared with healthy control subjects. Levels of C5 and C8 correlated with glycated haemoglobin (C5: r = 0.48, P = 0.019). After adjustment for BMI, glycated haemoglobin, age and gender, HNF4A-MODY and HNF1A patients had reduced levels of C5 and C8 compared with Type 2 diabetic patients (C5: P = 0.001; C8: P = 0.004). In addition, patients with HNF4A-MODY, but not those with HNF1A-MODY, had decreased TTR compared with diabetic patients (P = 0.038).


CONCLUSIONS
Serum concentrations of C5 and C8 seem to distinguish HNF4A and HNF1A-MODY from other forms of diabetes. However, hyperglycaemia per se increases the serum concentrations, thereby attenuating their potential role as biomarkers for MODY.
Department of Clinical Sciences/Diabetes and Endocrinology, Malmö University Hospital, Lund University, Malmö, Sweden. ella.karlsson@med.lu.se
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Shaat
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Groop
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D003182:Complement C5 / Q000378:metabolism; D003185:Complement C8 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000235:genetics; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011228:Prealbumin / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics
D015415:Biomarkers; D003182:Complement C5; D003185:Complement C8; C496487:HNF1A protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D011228:Prealbumin; D015534:Trans-Activators