S.F.ANG1, C.S.H.TAN1, L.X.GOH1, L.W.T.CHAN1, W.Y.C.KON2, R.F.VASANWALA3, W.J.LOW4, S.C.LIM1
Khoo Teck Puat Hospital1, Tan Tock Seng Hospital2, KK Women’s & Children’s Hospital3, Changi General Hospital4
Maturity-onset diabetes of the young (MODY) is a form of diabetes that is characterized by autosomal dominant inheritance, early-onset and lean body type. It is often misdiagnosed as Type 1 or Type 2 diabetes (T2D) due to their overlapping clinical features. Accurate diagnosis of MODY is important for precision medicine implementation. Therefore, we sought to evaluate the use of uric acid, a downstream transcription target of HNF4A, as a biomarker to identify potential patients with HNF4A-MODY for genetic testing.
As part of our young-onset research studies, eligible patients were subjected to MODY genetic testing. Patients were classified as having HNF4A-MODY if they harbor any likely pathogenic/pathogenic variant in HNF4A as annotated according to ACMG guidelines. Random plasma uric acid was measured using ELISA. Receiver operator curve (ROC) and precision recall curve (PRC) analyses were conducted for 287 patients (9 with HNF4A-MODY) with complete data.
Uric acid was lower in HNF4A-MODY (mean ± SD: 5.87 ± 1.67 vs 6.83 ± 1.70 mg/dL, p=0.05). Uric acid was investigated for its contribution to predict HNF4A status in combination with age, gender, ethnicity, BMI, HbA1c, systolic blood pressure, diabetes duration, HDL, triglyceride and presence of HNF4A T139I variant. Area under the curve (AUC) achieved was 0.863 (95% CI 0.707-1.000, p <0.001), with Gini index of 0.725 and maximum Kolmogorov-Smirnov (K-S) statistic of 0.734 at a cutoff of 0.042.
Plasma uric acid level can be utilized as a biomarker together with other clinical parameters to nominate young-onset T2D patients for genetic testing of HNF4A-MODY.