Association of glucokinase gene and glucokinase regulatory protein gene polymorphisms with gestational diabetes mellitus: A case-control study

Gene. 2022 May 25:824:146378. doi: 10.1016/j.gene.2022.146378. Epub 2022 Mar 8.

Abstract

Objectives: The aim of this study was to investigate the association of glucokinase (GCK) gene, glucokinase regulatory protein (GCKR) gene polymorphisms with the susceptibility to GDM in Chinese population.

Research design and methods: This case-control study included 835 GDM patients and 870 non-diabetic pregnant women who had their prenatal examinations at 24-28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. The nurses were trained to collect clinical information and blood samples. The candidate single nucleotide polymorphism (SNPs, GCK rs1799884, rs4607517, rs10278336, rs2268574, rs730497 and GCKR rs780094, rs1260326) were genotyped on Sequenom Massarray platform. Statistical analysis including independent sample t test, chi-square test, logistic regression and one-way ANOVA were performed to evaluate the differences in allele and genotype distributions and their correlations with the odds of GDM.

Results: There were statistically significant differences in age, pre-gestational BMI, education level and family history of diabetes between case and control group (P < 0.05). After adjusting for these confounders, GCK rs1799884 was still significantly associated with GDM (P < 0.05), but there were no significant associations between rs4607517, rs10278336 and rs2268574, rs780094 and rs1260326 polymorphisms and GDM odds (P > 0.05). In addition, the pregnant women with rs4607517 TT genotype had the significantly higher fasting blood glucose level than CC genotype (P < 0.05).

Conclusion: GCK rs1799884 mutation is associated with higher GDM odds in Chinese population. Further larger studies are needed to explore the association between GCK and GCKR polymorphisms and GDM susceptibility.

Keywords: Case–control study; Gestational diabetes mellitus (GDM); Glucokinase (GCK); Glucokinase regulatory protein (GCKR); Single nucleotide polymorphism (SNP).

MeSH terms

  • Carrier Proteins
  • Case-Control Studies
  • Child
  • Diabetes, Gestational* / genetics
  • Female
  • Glucokinase* / genetics
  • Humans
  • Polymorphism, Single Nucleotide
  • Pregnancy

Substances

  • Carrier Proteins
  • glucokinase regulatory protein
  • Glucokinase