P-309: Identificaton of maturity onset diabetes of the young among diabetic population of Karachi, Pakistan
E Abbas, A Fawwad, M A N SaqibAbstract
Introduction
Pakistan may have a substantial population of Maturity-onset diabetes of the young (MODY) who are frequently misdiagnosed as having type 1 or type 2 diabetes and mistreated.
Objectives
To identify MODY cases among type-I and type-II diabetics and to explore the validity of MODY Probability Calculator as comparable with the genetic findings.
Methods
1101 participants, both male and female, with type I and type II diabetes, diagnosed with diabetes at ≤ 35 years of age were included. An informed written consent was obtained from each participant. A standardized questionnaire covering anthropometric, clinical, biochemical, and lifestyle characteristics was used to gather data. The pancreatic autoantibodies were estimated through ELISA. The DNA of the subjects with all pancreatic autoantibody negative status was extracted and Whole Exome Sequencing (WES) was carried out at Endocrine Genetics Laboratory, McGill University, Quebec Canada. The FastQ file obtained from WES were analyzed through bioinformatics tools. Binary logistic regression analysis evaluated risk factors for negative GAD antibodies. Other statistical tests including chi square and independent t test were used to assess the associations. A p value <0.05 was considered significant.
Results
A total of 5,599 variants were obtained. A heterozygous missense variant in PDX1 gene (c13.G>A(p.Glu224Lys)), homozygous nonsense variants (c.1994G>A(p.Trp648Ter)) and a (c.1433 G>A(p.Trp478Ter)) were observed in in WFS1 gene. A heterozygous missense variant in EIF2AK4 (c.3143A>G(p.Asp1048Gly)) and a heterozygous frameshift variant (c.625-636del(p.Lys209GlyfsTer)) was found in PAX-6 gene. It was found that a significantly higher proportion of the MODY Score >70% was observed in subjects with all pancreatic autoantibodies (p<0.01).
Conclusions
Pathogenic variants in classical and non-classical MODY genes were present. The MODY Probability Calculator was found reliable in the study population.