Identification of a Novel -99A>T IAPP Gene Mutation in A North Indian Type-2-Diabetes Patient with HypertensionJayagandan Jayamani1*, Rajendra Prasad1 and Anil Bhansali2
- Corresponding Author:
- Dr. Rajendra Prasad
Professor & Head, Department of Biochemistry
Postgraduate Institute of Medical Education and Research
E-mail: [email protected]
Received Date: September 30, 2013; Accepted Date: November 19, 2013; Published Date: November 23, 2013
Citation: Jayamani J, Prasad R, Bhansali A (2013) Identification of a Novel -99A>T IAPP Gene Mutation in A North Indian Type-2-Diabetes Patient with Hypertension. J Diabetes Metab 4:314. doi: 10.4172/2155-6156.1000314
Copyright: © 2013 Jayamani J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Several studies conducted worldwide supports that mutations in activator domains of promoter region (ËÂ91 to ËÂ222 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 5ËÂËÂATTGGËÂ3ËÂ (corresponding to −101 to −97 of IAPP gene promoter) and its complementary sequence 3ËÂËÂTAACCËÂ5ËÂ 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.