Glucokinase Gene Mutations in Subjects with Gestational Diabetes Mellitus from Gaza Strip

Objective: This study was conducted in order to evaluate the frequency of GCK gene mutations in exons 7, 8 & 9 in women with Gestational Diabetes Mellitus (GDM) and their relationship to some biochemical parameters as compared to healthy controls.

Methods: Samples were collected from 45 GDM women and 42 apparently healthy pregnant women. DNA was extracted and the samples were screened for GCK exons 7, 8 & 9 mutations at positions C.682A>G (p.Thr228Ala); C.895G>C (p.Gly299Arg) and C.1148C>A (p.Ser383X), respectively. The mutations were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Investigated biochemical features included: fasting blood glucose (FBG), oral glucose tolerance test (OGTT), HbA1c, insulin and the lipid profile.

Results: The results showed that 9 out of the 45 (i.e., 20%) GDM subjects harbored the exon 8 (895G>C) mutation. Neither exon 7 (c.682A>G) nor exon 9 (c.1148C>A) was encountered in the study population. Moreover, the level of FBG, OGTT and HBA1c were higher in the c.895G>C mutation-positive subjects, as compared to mutation-negative ones.

Conclusions: The screening of GDM patients for GCK gene mutations allowed for the identification of glucokinase-deficient patients diagnosed as GDM. Therefore, molecular screening is important for the differential diagnosis of GDM and MODY2 and consequently, proper patient management.