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Common Type 2 Diabetes Risk Gene Variants Associate with Gestational Diabetes

Center for Pregnant Women with Diabetes (J.L., P.D.), Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark; Steno Diabetes Center (N.G., K.B.-J., O.P., T.H.), DK-2820 Gentofte, Denmark; Faculty of Health Sciences (P.D., T.J., O.P.), University of Copenhagen, DK-2100 Copenhagen, Denmark; Research Center for Prevention and Health (T.J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark; Faculty of Health Sciences (K.B.-J., O.P.), University of Aarhus, DK-8000 Aarhus, Denmark; and Faculty of Health Sciences (T.H.), University of Southern Denmark, DK-5000 Odenses C, Denmark

Address all correspondence and requests for reprints to: Jeannet Lauenborg, Faculty of Health Science, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen Ö, Denmark. E-mail: jeannet{at}lauenb.org.

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.