Abstract
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.
Highlights
Gestational Diabetes Mellitus (GDM) is defined as glucose intolerance resulting in hyperglycemia of variable severity with onset during pregnancy [1]
Polymorphisms in the promoter of GCK and polymorphisms of hepatocyte nuclear factor 1α (HNF1α) genes are common variants in Maturity-onset diabetes of the young (MODY) genes that increase the risk of GDM [3]
Heterozygous inactivating mutations in GCK are characterized by mild fasting hyperglycemia appearing at variable ages, while homozygous inactivating GCK mutations result in a more severe phenotype presenting at birth as permanent neonatal diabetes mellitus [5]
Summary
Gestational Diabetes Mellitus (GDM) is defined as glucose intolerance resulting in hyperglycemia of variable severity with onset during pregnancy [1]. GDM occurs if pancreatic β-cells are unable to face the increased insulin demand during pregnancy [2]. Polymorphisms in the promoter of GCK and polymorphisms of hepatocyte nuclear factor 1α (HNF1α) genes are common variants in Maturity-onset diabetes of the young (MODY) genes that increase the risk of GDM [3]. Glucokinase, termed glucose sensor, in pancreatic β-cells plays a crucial role in insulin secretion and regulation [4]. Heterozygous inactivating mutations in GCK are characterized by mild fasting hyperglycemia appearing at variable ages, while homozygous inactivating GCK mutations result in a more severe phenotype presenting at birth as permanent neonatal diabetes mellitus [5]
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