Common type 2 diabetes risk gene variants associate with gestational diabetes

J Clin Endocrinol Metab. 2009 Jan;94(1):145-50. doi: 10.1210/jc.2008-1336. Epub 2008 Nov 4.


Objective: We aimed to examine the association between gestational diabetes mellitus (GDM) and 11 recently identified type 2 diabetes susceptibility loci.

Research design and methods: Type 2 diabetes risk variants in TCF7L2, CDKAL1, SLC30A8, HHEX/IDE, CDKN2A/2B, IGF2BP2, FTO, TCF2, PPARG, KCNJ11, and WFS1 loci were genotyped in a cohort of women with a history of GDM (n = 283) and glucose-tolerant women of the population-based Inter99 cohort (n = 2446).

Results: All the risk alleles in the 11 examined type 2 diabetes risk variants showed an odds ratio (OR) greater than 1 for the GDM group compared with the control group ranging from 1.13 [95% confidence interval (CI) 0.88-1.46] to 1.44 (95% CI 1.19-1.74) except for the WFS1 rs10010131 variant with OR 0.87 (95% CI 0.73-1.05). Combined analysis of all 11 variants showed a highly significant additive effect of multiple risk alleles on risk of GDM [OR 1.18 (95% CI 1.10-1.27)] per risk allele, P = 3.2 x 10(-6)). Applying receiver-operating characteristic showed an area under the receiver-operating characteristic curve of 0.62 for the genetic test alone and 0.73 when combining information on age, body mass index, and genotypes of the 11 gene variants.

Conclusions: The prevalence in a prior GDM group of several previously proven type 2 diabetes risk alleles equals the findings from association studies on type 2 diabetes. This supports the hypothesis that GDM and type 2 diabetes are two of the same entity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes, Gestational / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Humans
  • Pregnancy
  • ROC Curve
  • Risk