Cho Y M, Kim T H, Lim S, Choi S H, Shin H D, Lee H K, Park K S, Jang H C
Department of Internal Medicine, College of Medicine, Seoul National University, 28 Yongon-Dong Chongno-Gu, Seoul 110-744, Korea.
Diabetologia. 2009 Feb;52(2):253-61. doi: 10.1007/s00125-008-1196-4. Epub 2008 Nov 11.
AIMS/HYPOTHESIS: New genetic variants associated with susceptibility to type 2 diabetes mellitus have been discovered in recent genome-wide association (GWA) studies. The aim of the present study was to examine the association between these diabetogenic variants and gestational diabetes mellitus (GDM).
The study included 869 Korean women with GDM and 345 female and 287 male Korean non-diabetic controls. We genotyped the single nucleotide polymorphisms (SNPs) rs7756992 and rs7754840 in CDKAL1; rs564398, rs1333040, rs10757278 and rs10811661 in the CDKN2A-CDKN2B region; rs8050136 in FTO; rs1111875, rs5015480 and rs7923837 in HHEX; rs4402960 in IGF2BP2; and rs13266634 in SLC30A8. In addition, rs7903146 and rs12255372 in TCF7L2; rs5215 and rs5219 in KCNJ11; and rs3856806 and rs1801282 in PPARG were genotyped. The genotype frequencies in the GDM patients were compared with those in the non-diabetic controls.
Compared with controls (men and women combined), GDM was associated with rs7756992 and rs7754840 (OR 1.55, 95% CI 1.34-1.79, p = 4.17 x 10(-9)) in CDKAL1; rs10811661 (OR 1.49, 95% CI 1.29-1.72, p = 1.05 x 10(-7)) in the CDKN2A-CDKN2B region; rs1111875 (OR 1.27, 95% CI 1.09-1.49, p = 0.003), rs5015480, and rs7923837 in HHEX; rs4402960 (OR 1.18, 95% CI 1.01-1.38, p = 0.03) in IGF2BP2; rs13266634 (OR 1.24, 95% CI 1.07-1.43, p = 0.005) in SLC30A8; and rs7903146 (OR 1.58, 95% CI 1.03-2.43, p = 0.038) in TCF7L2. The risk alleles of the SNPs rs7756992 and rs7754840 in CDKAL1; rs10811661 in the CDKN2A-CDKN2B region; and rs1111875, rs5015480 and rs7923837 in HHEX were associated with significant decreases in the insulin AUC during a 100 g OGTT performed at the time of diagnosis of GDM.
CONCLUSIONS/INTERPRETATION: Some of the type 2 diabetes-associated genetic variants that were discovered in the recent GWA studies are also associated with GDM in Koreans.
目的/假设：在近期的全基因组关联（GWA）研究中发现了与2型糖尿病易感性相关的新基因变异。本研究的目的是检验这些致糖尿病变异与妊娠期糖尿病（GDM）之间的关联。
该研究纳入了869名患有GDM的韩国女性以及345名韩国非糖尿病女性和287名韩国非糖尿病男性作为对照。我们对CDKAL1基因中的单核苷酸多态性（SNP）rs7756992和rs7754840；CDKN2A - CDKN2B区域中的rs564398、rs1333040、rs10757278和rs10811661；FTO基因中的rs8050136；HHEX基因中的rs1111875、rs5015480和rs7923837；IGF2BP2基因中的rs4402960；以及SLC30A8基因中的rs13266634进行基因分型。此外，还对TCF7L2基因中的rs7903146和rs12255372；KCNJ11基因中的rs5215和rs5219；以及PPARG基因中的rs3856806和rs1801282进行基因分型。将GDM患者的基因型频率与非糖尿病对照的基因型频率进行比较。
与对照组（男性和女性合并）相比，GDM与CDKAL1基因中的rs7756992和rs7754840（比值比[OR]1.55，95%置信区间[CI]1.34 - 1.79，p = 4.17×10⁻⁹）；CDKN2A - CDKN2B区域中的rs10811661（OR 1.49，95% CI 1.29 - 1.72，p = 1.05×10⁻⁷）；HHEX基因中的rs1111875（OR 1.27，95% CI 1.09 - 1.49，p = 0.003）、rs5015480和rs7923837；IGF2BP2基因中的rs4402960（OR 1.18，95% CI 1.01 - 1.38，p = 0.03）；SLC30A8基因中的rs13266634（OR 1.24，95% CI 1.07 - 1.43，p = 0.005）；以及TCF7L2基因中的rs7903146（OR 1.58，95% CI 1.03 - 2.43，p = 0.038）相关。CDKAL1基因中的SNP rs7756992和rs7754840；CDKN2A - CDKN2B区域中的rs10811661；以及HHEX基因中的rs1111875、rs5015480和rs7923837的风险等位基因与GDM诊断时进行的100 g口服葡萄糖耐量试验（OGTT）期间胰岛素曲线下面积（AUC）的显著降低相关。
结论/解读：近期GWA研究中发现 的一些与2型糖尿病相关的基因变异在韩国人中也与GDM相关。
