- •Maturity onset diabetes of young.
- •Gene mutations as cause of MODY focussed on HNF4α and GCK.
- •Evaluation of Clinical differences, and Pedigree analysis.
- •Screening of HNF4A and GCK gene mutations by RFLP and Sequencing.
- •Limitations of our research.
Maturity-onset Diabetes of Young (MODY) is a monogenic form of diabetes affecting 1–5% of young (often ≤25 years) diabetic patients exhibiting an autosomal dominant mode of inheritance. Considering the significance of genetic polymorphisms in a variety of diseases, this study aimed to determine the association between HNF4α and GCK gene polymorphisms and the risk of MODY in the Kashmir community, as well as their clinical differences.
The study was conducted on clinically confirmed MODY patients (n = 50), and age and gender-matched controls (25 T1DM and 25 non-diabetic) recruited from the endocrinology department of the hospital, for evaluating the HNF4α and GCK mutation. Under standard conditions, PCR-mediated amplification was done to evaluate the respective exons. Preliminary mutations were detected using restriction enzymes (BfaI and HhaI), which were then followed by sequencing of representative samples. The diabetic history, clinical and biochemical data were obtained after proper consent.
Our data revealed no association of HNF4α (exon7) and GCK (exon8) gene mutation with MODY disease susceptibility in the Kashmiri population. On diagnosis, no MODY patient was given immediate insulin; instead, metformin (68%) or sulphonyl-urea (28%) and dietary changes (4%) were recommended. Later in life, 54% of MODY patients develop insulin dependency. The MODY probability was calculated to be 73.88% (±4.56). HbA1c levels were lower [7.48% (±1.64)] than in T1DM [9.17(±2.29%)].
Young early-onset diabetic patients were able to keep their HbA1c and blood glucose levels stable with a modified diet and metformin/sulphonyl-urea, but they may become insulin-dependent in the future, as seen in our study. As a result, prompt diagnosis and management are essential for avoiding complications. Furthermore, no HNF4α (exon7) or GCK (exon 8) mutations were found in MODY patients or T1DM/healthy non-diabetic controls.
Abbreviations:MODY (Maturity-onset diabetes of the young), HNF4α (hepatocyte nuclear factor 4 alpha), HNF1α (hepatocyte nuclear factor alpha 1), GCK (Glucokinase), GDM (Gestational diabetes mellitus), PCR (polymerase chain reaction), RFLP (Restriction fragment length polymorphism), T1D (Type1 diabetes)
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Published online: February 04, 2022
Accepted: January 23, 2022
Received in revised form: January 14, 2022
Received: October 12, 2021
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