TY - JOUR

T1 - Common type 2 diabetes risk gene variants associate with gestational diabetes

AU - Lauenborg, Jeannet

AU - Grarup, Niels

AU - Damm, Peter

AU - Borch-Johnsen, Knut

AU - Jørgensen, Torben

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Lauenborg, Jeannet

AU - Grarup, Niels

AU - Damm, Peter

AU - Borch-Johnsen, Knut

AU - Jørgensen, Torben

AU - Pedersen, Oluf

AU - Hansen, Torben

PY - 2009/1/1

Y1 - 2009/1/1

N2 - Objective: We aimed to examine the association between gestational diabetes (GDM) and eleven 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 in glucose tolerant women of the population-based Inter99 cohort (n=2,446). Results: All the risk alleles in the 11 examined type 2 diabetes risk variants showed an odds ratio greater than 1 for the GDM group compared to the control group ranging from 1.13 (95% 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=3.2x10(-6)). Applying receiver operating characteristic (ROC) showed an area under the ROC curve of 0.62 for the genetic test alone and 0.73 when combining information on age, BMI and genotypes of the eleven 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.

AB - Objective: We aimed to examine the association between gestational diabetes (GDM) and eleven 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 in glucose tolerant women of the population-based Inter99 cohort (n=2,446). Results: All the risk alleles in the 11 examined type 2 diabetes risk variants showed an odds ratio greater than 1 for the GDM group compared to the control group ranging from 1.13 (95% 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=3.2x10(-6)). Applying receiver operating characteristic (ROC) showed an area under the ROC curve of 0.62 for the genetic test alone and 0.73 when combining information on age, BMI and genotypes of the eleven 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.

U2 - 10.1210/jc.2008-1336

DO - 10.1210/jc.2008-1336

M3 - Journal article

C2 - 18984664

VL - 94

SP - 145

EP - 150

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -