Genetic linkage analysis of GCK and HNF1A genes in a group of families with MODY in Isfahan province

Diabetes mellitus is a group of metabolic disorders resulting in increased level of blood sugar. Type 1 Diabetes (T1D), Type 2 Diabetes (T2D) and monogenic diabetes are there major groups of diabetes. Maturity-onset diabetes of the young (MODY) is a monogenic diabetes that is frequently mistaken for T1D or T2D and it has 14 different subgroups. The aim of this study was to diagnose MODY and determine the frequency of its 2 major subgroups in Isfahan diabetic population.

In this descriptive-experimental study with the aim of determining type and the frequency of mutations in GCK and HNF1A genes in 26 families with MODY from Isfahan using genetic linkage analysis method and select of 4 markers for each gene. Linkage results was confirmed by fragment analysis and then all the exons of genes were sequenced in any linked families.

In this study from 26 families, 4 families were linked to markers of GCK gene and 3 families were linked to HNF1A gene. After sequencing of all exons of these 2 genes in the related families, variants were analyzed and their effects on diabetes were surveyed. There was no pathogenic mutation but some polymorphisms with increasing effects on susceptibility to diabetes were found.

in this study despite of the fact that some families were linked to markers of these 2 gene, and the results of other studies that mutations in these 2 genes are the frequent reasons of MODY, there were any pathogenic variant in any of the patients. So it seems that the genetic profile of this population is different from other studied populations.