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). METHODS: 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. RESULTS: 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。 方法：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。 结果：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。
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