Common type 2 diabetes risk gene variants associate with gestational diabetes.
OBJECTIVE
We aimed to examine the association between gestational diabetes mellitus (GDM) and 11 recently identified type 2 diabetes susceptibility loci.


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.
Lauenborg
Jeannet
J
Center for Pregnant Women with Diabetes, Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark. jeannet@lauenb.org
Grarup
Niels
N
Damm
Peter
P
Borch-Johnsen
Knut
K
Jørgensen
Torben
T
Pedersen
Oluf
O
Hansen
Torben
T
D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics*; D016640:Diabetes, Gestational / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D011247:Pregnancy; D012372:ROC Curve; D012306:Risk