Jayagandan Jayamani, Rajendra Prasad and Anil Bhansali
Several studies conducted worldwide supports that mutations in activator domains of promoter region (Ë—91 to Ë—222 bp) of IAPP gene can lead to increased Islet amyloid deposition, ß cells destruction and insulin resistance. Considering it a pilot study was conducted to identify amylin promoter mutation and its association in patients diagnosed having both type-2-diabetes and hypertension. Strikingly we identified a novel −99A>T mutation in a 35 year old female patient with BMI of 26.4 kg/m² and family history of diabetes and hypertension. To elucidate whether the identified mutation disrupts the binding site for transcription factors, potential binding sites in the vicinity of this mutation was screened for using the TESS master (Transcription Element Search System) a computer program on TRANSFAC, EMBL, CBIL databases. This −99A>T mutation produced a sequence 5ˈ˗ATTGGË—3ˈ (corresponding to −101 to −97 of IAPP gene promoter) and its complementary sequence 3ˈ˗TAACCË—5ˈ formed a putative binding site for CAAT box binding transcription factors (CTF) like CBP, CP-1, C/EBPα. All these CTFs are well established transcription activators, their role in initiation and maintaining efficiency of eukaryotic transcription is also very well established. This activator domain −99A>T mutation of IAPP gene can possibly increase gene transcription, production, deposition of Islet amyloid ultimately leading to pathogenesis of type-2-diabetes.
