Clinical profiling and screening for HNF4α and GCK gene mutations in Kashmiri patients with maturity-onset diabetes of the young (MODY).

AIM: 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. METHOD: 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. RESULTS: 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%)]. CONCLUSIONS: 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.

Genetic Testing of Maturity-Onset Diabetes of the Young Current Status and Future Perspectives.

Diabetes is a global epidemic problem growing exponentially in Asian countries posing a serious threat. Among diabetes, maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic disorders that occurs due to ß cell dysfunction. Genetic defects in the pancreatic ß-cells result in the decrease of insulin production required for glucose utilization thereby lead to early-onset diabetes (often <25 years). It is generally considered as non-insulin dependent form of diabetes and comprises of 1-5% of total diabetes. Till date, 14 genes have been identified and mutation in them may lead to MODY. Different genetic testing methodologies like linkage analysis, restriction fragment length polymorphism, and DNA sequencing are used for the accurate and correct investigation of gene mutations associated with MODY. The next-generation sequencing has emerged as one of the most promising and effective tools to identify novel mutated genes related to MODY. Diagnosis of MODY is mainly relying on the sequential screening of the three marker genes like hepatocyte nuclear factor 1 alpha (HNF1α), hepatocyte nuclear factor 4 alpha (HNF4α), and glucokinase (GCK). Interestingly, MODY patients can be managed by diet alone for many years and may also require minimal doses of sulfonylureas. The primary objective of this article is to provide a review on current status of MODY, its prevalence, genetic testing/diagnosis, possible treatment, and future perspective.

Fish antimicrobial peptides (AMP's) as essential and promising molecular therapeutic agents: A review.

Antimicrobial peptides (AMPs) are generally considered as an essential component of innate immunity, thereby providing the first line of defense against wide range of pathogens. In addition, they can also kill the pathogens which are generally resistant to number of antibiotics, thereby providing the avenues for the development of future therapeutic agents. Fishes are constantly challenged by variety of pathogens which not only shows detrimental effect on their health but also increases risk of becoming resistant to conventional antibiotics. As fishes rely more on innate immunity, AMPs can serve as a potential defensive weapons in fishes for combating emerging devastating diseases. Generally, AMPs show multidimensional properties like rapid diffusion to the site of infection, recruitment of other immune cells to infected tissues and vigorous potential to rapidly neutralize broad range of pathogens (bacterial, fungal and viral). AMPs also exhibit diverse biological effect like endotoxin neutralization, immunomodulation and induction of angiogenesis in mammals. Due to these properties AMPs have become one of the most promising therapeutic agents to be studied. Till date, many AMPs have been isolated from the fishes but not fully characterized at molecular level. This review provides an overview of the structures, functions, and putative mechanisms of major families of fish AMPs. Further, we also highlighted how fish AMPs can be used as a novel therapeutic tool which is the theme of future research in drug development.