Increased C282Y heterozygosity in gestational diabetes

Fetal Diagn Ther. 2005 Sep-Oct;20(5):349-54. doi: 10.1159/000086811.


Background: Hereditary hemochromatosis is an autosomal recessive disorder of iron metabolism that is characterized by excess accumulation of iron in various organs and often leads to diabetes mellitus (DM). To study whether mutations in the hemochromatosis gene (HFE) could be a risk factor for the development of gestational diabetes mellitus (GDM), the prevalence of HFE mutations in patients with GDM was compared to that of healthy pregnant controls.

Methods: GDM was diagnosed in 208 of 2,421 pregnant woman screened between the 24th and 28th week of gestation over a period of 18 months. Patients and 170 matched control subjects were screened for the HFE gene mutations C282Y and H63D.

Results: In North and Central European GDM patients, the allele frequency of the C282Y mutation (7.7%) was higher than in pregnant controls (2.9%; p = 0.04), while the frequency of the H63D mutation was not different (p = 0.45). Three patients with GDM were homozygous for H63D (3.1%), 1 patient was homozygous for C282Y (1.0%), 2 patients were compound heterozygous (2.0%) and 26 were heterozygous [11 C282Y (11.2%) and 15 H63D (15.3%)]. C282Y and H63D allele frequencies were not different between controls and GDM patients of Southern European or non-European origin. Irrespective of the HFE-mutation status, serum ferritin levels were increased in patients with GDM compared to healthy pregnant controls (p = 0.01), while transferrin saturation was similar in both groups.

Conclusions: In North and Central European patients with GDM, the C282Y allele frequency is higher than in healthy pregnant women, suggesting a genetic susceptibility to the development of GDM.

MeSH terms

  • Adolescent
  • Adult
  • Diabetes, Gestational / epidemiology*
  • Diabetes, Gestational / genetics*
  • Europe / epidemiology
  • Female
  • Ferritins / blood
  • Gene Frequency
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease / epidemiology
  • Hemochromatosis Protein
  • Heterozygote*
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Membrane Proteins / genetics*
  • Point Mutation
  • Pregnancy
  • Prevalence
  • Risk Factors


  • HFE protein, human
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Ferritins