Can complement factors 5 and 8 and transthyretin be used as biomarkers for MODY 1 (HNF4A‐MODY) and MODY 3 (HNF1A‐MODY)?

AbstractAims  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)‐1α and HNF‐4α 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‐1α (n = 29) and ΗΝF‐4α (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.