Lauenborg Jeannet, Grarup Niels, Damm Peter, Borch-Johnsen Knut, Jørgensen Torben, Pedersen Oluf, Hansen Torben
Center for Pregnant Women with Diabetes, Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, DK-2100 Copenhagen, Denmark.
J Clin Endocrinol Metab. 2009 Jan;94(1):145-50. doi: 10.1210/jc.2008-1336. Epub 2008 Nov 4.
We aimed to examine the association between gestational diabetes mellitus (GDM) and 11 recently identified type 2 diabetes susceptibility loci.
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).
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.
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.
我们旨在研究妊娠糖尿病（GDM）与最近确定的11个2型糖尿病易感基因座之间的关联。
对一组有GDM病史的女性（n = 283）和基于人群的Inter99队列中的糖耐量正常女性（n = 2446），对TCF7L2、CDKAL1、SLC30A8、HHEX/IDE、CDKN2A/2B、IGF2BP2、FTO、TCF2、PPARG、KCNJ11和WFS1基因座中的2型糖尿病风险变异进行基因分型。
与对照组相比，11个检测的2型糖尿病风险变异中的所有风险等位基因在GDM组中的比值比（OR）均大于1，范围从1.13[95%置信区间（CI）0.88 - 1.46]到1.44（95% CI 1.19 - 1.74），除了WFS1 rs10010131变异，其OR为0.87（95% CI 0.73 - 1.05）。对所有11个变异进行联合分析显示，每个风险等位基因对GDM风险有高度显著的多风险等位基因累加效应[OR 1.18（95% CI 1.10 - 1.27）]，P = 3.2×10⁻⁶）。应用受试者工作特征曲线分析显示，仅基因检测时受试者工作特征曲线下面积为0.62，结合年龄、体重指数和11个基因变异的基因型信息时为0.73。
先前GDM组中几种先前已证实的2型糖尿病风险等位基因的患病率与2型糖尿病关联研究的结果相当。这支持了GDM和2型糖尿病是同一实体的两种表现这一假设。
