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Diabetologia
Published in: Diabetologia 2/2009

01-02-2009 | Article

Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population

Authors: Y. M. Cho, T. H. Kim, S. Lim, S. H. Choi, H. D. Shin, H. K. Lee, K. S. Park, H. C. Jang

Published in: Diabetologia | Issue 2/2009

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Abstract

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 × 10−9) in CDKAL1; rs10811661 (OR 1.49, 95% CI 1.29–1.72, p = 1.05 × 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.
Appendix
Available only for authorised users
Literature
1.
Metzger BE (1991) Summary and recommendations of the Third International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes 40(Suppl 2):197–201PubMed
2.
Amankwah KS, Prentice RL, Fleury FJ (1977) The incidence of gestational diabetes. Obstet Gynecol 49:497–498PubMed
3.
Jang HC, Cho NH, Jung KB, Oh KS, Dooley SL, Metzger BE (1995) Screening for gestational diabetes mellitus in Korea. Int J Gynaecol Obstet 51:115–122PubMedCrossRef
4.
5.
McLellan JA, Barrow BA, Levy JC et al (1995) Prevalence of diabetes mellitus and impaired glucose tolerance in parents of women with gestational diabetes. Diabetologia 38:693–698PubMedCrossRef
6.
Martin AO, Simpson JL, Ober C, Freinkel N (1985) Frequency of diabetes mellitus in mothers of probands with gestational diabetes: possible maternal influence on the predisposition to gestational diabetes. Am J Obstet Gynecol 151:471–475PubMed
7.
Buchanan TA, Xiang AH (2005) Gestational diabetes mellitus. J Clin Invest 115:485–491PubMed
8.
Kim C, Newton KM, Knopp RH (2002) Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care 25:1862–1868PubMedCrossRef
9.
O’Sullivan JB, Mahan CM (1964) Criteria for the oral glucose tolerance test in pregnancy. Diabetes 13:278–285PubMed
10.
Robitaille J, Grant AM (2008) The genetics of gestational diabetes mellitus: evidence for relationship with type 2 diabetes mellitus. Genet Med 10:240–250PubMedCrossRef
11.
Zaidi FK, Wareham NJ, McCarthy MI et al (1997) Homozygosity for a common polymorphism in the islet-specific promoter of the glucokinase gene is associated with a reduced early insulin response to oral glucose in pregnant women. Diabet Med 14:228–234PubMedCrossRef
12.
Leipold H, Knofler M, Gruber C, Haslinger P, Bancher-Todesca D, Worda C (2004) Calpain-10 haplotype combination and association with gestational diabetes mellitus. Obstet Gynecol 103:1235–1240PubMed
13.
Rissanen J, Markkanen A, Karkkainen P et al (2000) Sulfonylurea receptor 1 gene variants are associated with gestational diabetes and type 2 diabetes but not with altered secretion of insulin. Diabetes Care 23:70–73PubMedCrossRef
14.
Shaat N, Ekelund M, Lernmark A et al (2005) Association of the E23K polymorphism in the KCNJ11 gene with gestational diabetes mellitus. Diabetologia 48:2544–2551PubMedCrossRef
15.
Festa A, Krugluger W, Shnawa N, Hopmeier P, Haffner SM, Schernthaner G (1999) Trp64Arg polymorphism of the β3-adrenergic receptor gene in pregnancy: association with mild gestational diabetes mellitus. J Clin Endocrinol Metab 84:1695–1699PubMedCrossRef
16.
Leipold H, Knoefler M, Gruber C, Klein K, Haslinger P, Worda C (2006) Plasminogen activator inhibitor 1 gene polymorphism and gestational diabetes mellitus. Obstet Gynecol 107:651–656PubMed
17.
Shaat N, Lernmark A, Karlsson E et al (2007) A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus. Diabetologia 50:972–979PubMedCrossRef
18.
Watanabe RM, Allayee H, Xiang AH et al (2007) Transcription factor 7-like 2 (TCF7L2) is associated with gestational diabetes mellitus and interacts with adiposity to alter insulin secretion in Mexican Americans. Diabetes 56:1481–1485PubMedCrossRef
19.
Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678CrossRef
20.
Saxena R, Voight BF, Lyssenko V et al (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331–1336PubMedCrossRef
21.
Scott LJ, Mohlke KL, Bonnycastle LL et al (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341–1345PubMedCrossRef
22.
Sladek R, Rocheleau G, Rung J et al (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881–885PubMedCrossRef
23.
Zeggini E, Weedon MN, Lindgren CM et al (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316:1336–1341PubMedCrossRef
24.
Frayling TM (2007) Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genet 8:657–662PubMedCrossRef
25.
Ng MC, Park KS, Oh B et al (2008) Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2 and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes 57:2226–2233PubMedCrossRef
26.
Jang HC, Cho NH, Min YK, Han IK, Jung KB, Metzger BE (1997) Increased macrosomia and perinatal morbidity independent of maternal obesity and advanced age in Korean women with GDM. Diabetes Care 20:1582–1588PubMedCrossRef
27.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef
28.
Helgadottir A, Thorleifsson G, Manolescu A et al (2007) A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 316:1491–1493PubMedCrossRef
29.
McPherson R, Pertsemlidis A, Kavaslar N et al (2007) A common allele on chromosome 9 associated with coronary heart disease. Science 316:1488–1491PubMedCrossRef
30.
Samani NJ, Erdmann J, Hall AS et al (2007) Genomewide association analysis of coronary artery disease. N Engl J Med 357:443–453PubMedCrossRef
31.
Grant SF, Thorleifsson G, Reynisdottir I et al (2006) Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 38:320–323PubMedCrossRef
32.
Koo BK, Cho YM, Park BL et al (2007) Polymorphisms of KCNJ11 (Kir6.2 gene) are associated with type 2 diabetes and hypertension in the Korean population. Diabet Med 24:178–186PubMedCrossRef
33.
Moon MK, Cho YM, Jung HS et al (2005) Genetic polymorphisms in peroxisome proliferator-activated receptor gamma are associated with type 2 diabetes mellitus and obesity in the Korean population. Diabet Med 22:1161–1166PubMedCrossRef
34.
Horikoshi M, Hara K, Ito C et al (2007) Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population. Diabetologia 50:2461–2466PubMedCrossRef
35.
Karnik SK, Chen H, McLean GW et al (2007) Menin controls growth of pancreatic beta-cells in pregnant mice and promotes gestational diabetes mellitus. Science 318:806–809PubMedCrossRef
36.
Buchanan TA (2001) Pancreatic B-cell defects in gestational diabetes: implications for the pathogenesis and prevention of type 2 diabetes. J Clin Endocrinol Metab 86:989–993PubMedCrossRef
37.
Kautzky-Willer A, Prager R, Waldhausl W et al (1997) Pronounced insulin resistance and inadequate beta-cell secretion characterize lean gestational diabetes during and after pregnancy. Diabetes Care 20:1717–1723PubMedCrossRef
38.
Ryan EA, Imes S, Liu D et al (1995) Defects in insulin secretion and action in women with a history of gestational diabetes. Diabetes 44:506–512PubMedCrossRef
39.
Ubeda M, Rukstalis JM, Habener JF (2006) Inhibition of cyclin-dependent kinase 5 activity protects pancreatic beta cells from glucotoxicity. J Biol Chem 281:28858–28864PubMedCrossRef
40.
Wei FY, Nagashima K, Ohshima T et al (2005) Cdk5-dependent regulation of glucose-stimulated insulin secretion. Nat Med 11:1104–1108PubMedCrossRef
41.
Krishnamurthy J, Ramsey MR, Ligon KL et al (2006) p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443:453–457PubMedCrossRef
42.
Marzo N, Mora C, Fabregat ME et al (2004) Pancreatic islets from cyclin-dependent kinase 4/R24C (Cdk4) knockin mice have significantly increased beta cell mass and are physiologically functional, indicating that Cdk4 is a potential target for pancreatic beta cell mass regeneration in type 1 diabetes. Diabetologia 47:686–694PubMedCrossRef
43.
Mettus RV, Rane SG (2003) Characterization of the abnormal pancreatic development, reduced growth and infertility in Cdk4 mutant mice. Oncogene 22:8413–8421PubMedCrossRef
44.
Rane SG, Dubus P, Mettus RV et al (1999) Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in β-islet cell hyperplasia. Nat Genet 22:44–52PubMedCrossRef
45.
Moritani M, Yamasaki S, Kagami M et al (2005) Hypoplasia of endocrine and exocrine pancreas in homozygous transgenic TGF-β1. Mol Cell Endocrinol 229:175–184PubMedCrossRef
46.
Bort R, Martinez-Barbera JP, Beddington RS, Zaret KS (2004) Hex homeobox gene-dependent tissue positioning is required for organogenesis of the ventral pancreas. Development 131:797–806PubMedCrossRef
47.
Steinthorsdottir V, Thorleifsson G, Reynisdottir I et al (2007) A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet 39:770–775PubMedCrossRef
Metadata
Title
Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population
Authors
Y. M. Cho
T. H. Kim
S. Lim
S. H. Choi
H. D. Shin
H. K. Lee
K. S. Park
H. C. Jang
Publication date
01-02-2009
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 2/2009
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-008-1196-4

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