The aim of this study was to perform metabolic profiling in urine from patients with MODY due to mutations in the genes encoding glucokinase (GCK) or hepatocyte nuclear factor 1 alpha (HNF1A), type 2 diabetes (T2D) and normoglycaemic control subjects.
Highly sensitive C-reactive protein (hsCRP) was low in the proband and her father (≤0.1 mg/l) indicating that type 2 diabetes was unlikely, and that hepatocyte nuclear factor 1-α-maturity onset diabetes of the young (HNF1A-MODY) was the most likely diagnosis.
In view of her presentation at such a young age and strong family history, a possibility of maturity onset diabetes in young was considered and the genetic test confirmed hepatocyte nuclear factor-1 α mutation on chromosome 12.
Nominally significant association (P<0.05) was observed for markers in: TCF7L2, RBMS1, CDKAL1, ZNF239, KCNQ1 and TCF1 and a significant bias (P<0.05) towards OR>1 was observed for markers selected from previous T2D genome-wide association studies, consistent with a role for Old World variants in susceptibility to T2D in Latin Americans.
We initially examined 51 HNF1A-MODY patients, 56 subjects with type 1 diabetes (T1DM), 39 with type 2 diabetes (T2DM) and 43 non-diabetic individuals (ND) from Poland.
One region, upstream of the gene FAM78B, contains three binding sites for the transcription factor PPARG and two binding sites for HNF1A, both previously implicated in the pathology of type 2 diabetes.
hs-CRP was lower in HNF1A-MODY (median [IQR] 0.3 [0.1-0.6] mg/L) than type 2 diabetes (1.40 [0.60-3.45] mg/L; P < 0.001) and type 1 diabetes (1.10 [0.50-1.85] mg/L; P < 0.001), HNF4A-MODY (1.45 [0.46-2.88] mg/L; P < 0.001), GCK-MODY (0.60 [0.30-1.80] mg/L; P < 0.001), and HNF1B-MODY (0.60 [0.10-2.8] mg/L; P = 0.07). hs-CRP discriminated HNF1A-MODY from type 2 diabetes with hs-CRP <0.75 mg/L showing 79% sensitivity and 70% specificity (receiver operating characteristic area under the curve = 0.84).
Receiver operating characteristic (ROC) curves were used to identify optimal UCPCR cutoffs to differentiate HNF1A/4A MODY from type 1 and type 2 diabetes.
The HNF1AG319S carrier status was associated with incident type 2 diabetes (odds ratio [OR] 3.78 [95% CI 2.13-6.69]) after adjustment for age, sex, hypertension, triglyceride, HDL cholesterol, and waist circumference.
We aimed to investigate whether CRP was mediating the association between HNF1AG319S and type 2 diabetes in an Aboriginal Canadian population with a high prevalence of diabetes.
Occasional difficulties may be encountered when classifying patients with MODY-2, MODY-3 or type 2 diabetes of atypical characteristics, in this case patients who present I27L polymorphism in the HNF1alpha gene.
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.
We conclude that low frequency, nonsynonymous coding variants in the terminal exons of HNF1A are unlikely to contribute to T2D-susceptibility in European samples.
Type 2 diabetes mellitus (T2DM) is a genetically heterogeneous disease, hepatocyte nuclear factor-1 homeobox A (HNF1A) single-nucleotide polymorphisms (SNPs) playing a minor role in its pathogenesis.