Common Polymorphisms Identified In Patients with Type 2 Diabetes Mellitus Revealed From Next-Generation Sequencing Analysis

Fateme  Sefid; Ghasem  Azamirad; Samira  Asadollahi; Seyed Mehdi  Kalantar; Saeed Hosein  Khalilzade; Mohammad Yahya  Vahidi Mehrjardi

doi:10.18502/ijdo.v15i2.12964

Fateme Sefid Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Ghasem Azamirad Department of Mechanical Engineering, Yazd University, Yazd, Iran.
Samira Asadollahi Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Seyed Mehdi Kalantar Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Saeed Hosein Khalilzade Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Mohammad Yahya Vahidi Mehrjardi Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

DOI: https://doi.org/10.18502/ijdo.v15i2.12964

Keywords: diabetes mellitus, Type 2, Next generation sequencing

Abstract

Objective: Type 2 diabetes mellitus (T2DM) is a multifactorial genetic condition caused by the combination of genes and environmental factors. Several variations linked to T2DM have been discovered in recent genetic investigations, particularly genome-wide association studies (GWAS). This study aimed to investigate genes involved in T2DM, focusing on the NGS analysis and studying the genetic basis of T2DM to improve diagnosis, prevention, and treatment.

Materials and Methods: We selected 5 families based on the diagnosis of diabetes at the age of 30 years or earlier in at least 3 consecutive generations for NGS analyses.

Results: For each of the 5 participants tested thus far, a mean of 11 to 21 variants of clinical significance were detected. These variants were located in different genes, which indicate the association of these genes with susceptibility to diabetes. WFS1 and INS gene mutations were present in all five diabetic patients analyzed. Specifically, mutations in WFS1, KCNJ11, ABCC8, HNF1B, INS, GCKR, HNF1A and PCSK1N account for 25%, 13%, 8%, 7%, 7%, 6%, 6% and 6% of patients, respectively.

Conclusion: WFS1 is the most often altered gene in our participants with putative alterations, according to our findings (25%). WFS1 mutations were discovered in all of the probands.