Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population
Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population
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DOI：
10.1007/s00125-008-1196-4
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发表时间：
2009-02-01
期刊：
影响因子：
8.2
通讯作者：
Jang, H. C.
中科院分区：
文献类型：
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作者：
Cho, Y. M.;Kim, T. H.;Jang, H. C.
在最近的全基因组关联（GWA）研究中发现了与2型糖尿病易感性相关的新的遗传变异。本研究的目的是探讨这些糖尿病基因变异与妊娠期糖尿病（GDM）之间的关系，该研究包括869名韩国GDM妇女和345名女性和287名男性韩国非糖尿病对照。我们对CDKAL 1基因的rs7756992和rs7754840，CDKN 2A-CDKN 2B区域的rs 564398、rs 1333040、rs 10757278和rs 10811661，FTO基因的rs 8050136，HHEX基因的rs 1111875、rs 5015480和rs7923837，IGF 2BP 2基因的rs 4402960，和SLC 30 A8中的rs 13266634。此外，还对TCF 7 L2的rs7903146和rs 12255372、KCNJ 11的rs 5215和rs 5219以及PPARG的rs3856806和rs 1801282进行了基因分型。比较GDM组与非糖尿病对照组的基因型频率（男性和女性合并），GDM与rs7756992和rs7754840相关CDKAL1（OR 1.55，95% CI 1.34-1.79，p = 4.17 x 10（-9））; rs10811661（OR 1.49，95% CI 1.29-1.72，p = 1.05 x 10（-7））在CDKN 2A-CDKN 2B区域; rs 1111875（OR 1.27，95% CI 1.09-1.49，p = 0.003），HHEX中rs 5015480和rs7923837; rs 4402960 IGF2BP 2（OR 1.18，95% CI 1.01-1.38，p = 0.03）; rs13266634 SLC 30 A8中rs7903146（OR 1.24，95%CI 1.07-1.43，p = 0.005）; TCF 7 L2中rs7903146（OR 1.58，95%CI 1.03-2.43，p = 0.038）。CDKAL 1基因的rs7756992和rs7754840、CDKN 2A-CDKN 2B区域的rs 10811661、CDKN 2A-CDKN 2B区域的rs 1081116661、CDKN 2A-CDKN 2B区域的rs 108111661616616和RS 1111875，HHEX中的rs 5015480和rs7923837与在诊断GDM时进行的100 g OGTT期间胰岛素AUC的显著降低相关。在最近的GWA研究中发现的相关遗传变异也与韩国人的GDM有关。
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.Some of the type 2 diabetes-associated genetic variants that were discovered in the recent GWA studies are also associated with GDM in Koreans.