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PMID: 19002430 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Diabetologia ·Vol. 52 ·No. 2 ·2009-02-00 ·Pages 253-61

Cho YM, Kim TH, Lim S, Choi SH, Shin HD, Lee HK, Park KS, Jang HC

Abstract

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.

MeSH Terms
Alpha-Ketoglutarate-Dependent Dioxygenase FTO Chromosome Mapping Diabetes Mellitus, Type 2/genetics Diabetes, Gestational/genetics Female Genetic Variation Genome, Human Genome-Wide Association Study Humans Korea Male Polymorphism, Single Nucleotide Pregnancy Proteins/genetics RNA-Binding Proteins/genetics
Chemicals
IGF2BP2 protein, human Proteins RNA-Binding Proteins Alpha-Ketoglutarate-Dependent Dioxygenase FTO FTO protein, human
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Cho Y M
Department of Internal Medicine, College of Medicine, Seoul National University, 28 Yongon-Dong Chongno-Gu, Seoul 110-744, Korea.
Kim T H
Lim S
Choi S H
Shin H D
Lee H K
Park K S
Jang H C
References (47)
47 references, click to expand
  1. Screening for gestational diabetes mellitus in Korea.
    Int J Gynaecol Obstet. 1995 Nov;51(2):115-22 PMID: 8635631
  2. Hypoplasia of endocrine and exocrine pancreas in homozygous transgenic TGF-beta1.
    Mol Cell Endocrinol. 2005 Jan 14;229(1-2):175-84 PMID: 15607541
  3. Polymorphisms of KCNJ11 (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population.
    Diabet Med. 2007 Feb;24(2):178-86 PMID: 17257281
  4. Defects in insulin secretion and action in women with a history of gestational diabetes.
    Diabetes. 1995 May;44(5):506-12 PMID: 7729607
  5. Increased macrosomia and perinatal morbidity independent of maternal obesity and advanced age in Korean women with GDM.
    Diabetes Care. 1997 Oct;20(10):1582-8 PMID: 9314639
  6. Characterization of the abnormal pancreatic development, reduced growth and infertility in Cdk4 mutant mice.
    Oncogene. 2003 Nov 20;22(52):8413-21 PMID: 14627982
  7. Plasminogen activator inhibitor 1 gene polymorphism and gestational diabetes mellitus.
    Obstet Gynecol. 2006 Mar;107(3):651-6 PMID: 16507937
  8. Calpain-10 haplotype combination and association with gestational diabetes mellitus.
    Obstet Gynecol. 2004 Jun;103(6):1235-40 PMID: 15172858
  9. 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. 2004 Apr;47(4):686-94 PMID: 15298346
  10. Cdk5-dependent regulation of glucose-stimulated insulin secretion.
    Nat Med. 2005 Oct;11(10):1104-8 PMID: 16155576
  11. 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. 1997 Mar;14(3):228-34 PMID: 9088772
  12. A common allele on chromosome 9 associated with coronary heart disease.
    Science. 2007 Jun 8;316(5830):1488-91 PMID: 17478681
  13. Genome-wide association studies provide new insights into type 2 diabetes aetiology.
    Nat Rev Genet. 2007 Sep;8(9):657-62 PMID: 17703236
  14. Association of the E23K polymorphism in the KCNJ11 gene with gestational diabetes mellitus.
    Diabetologia. 2005 Dec;48(12):2544-51 PMID: 16320083
  15. Sulfonylurea receptor 1 gene variants are associated with gestational diabetes and type 2 diabetes but not with altered secretion of insulin.
    Diabetes Care. 2000 Jan;23(1):70-3 PMID: 10857971
  16. Hex homeobox gene-dependent tissue positioning is required for organogenesis of the ventral pancreas.
    Development. 2004 Feb;131(4):797-806 PMID: 14736744
  17. Pancreatic B-cell defects in gestational diabetes: implications for the pathogenesis and prevention of type 2 diabetes.
    J Clin Endocrinol Metab. 2001 Mar;86(3):989-93 PMID: 11238474
  18. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.
    Science. 2007 Jun 1;316(5829):1341-5 PMID: 17463248
  19. Menin controls growth of pancreatic beta-cells in pregnant mice and promotes gestational diabetes mellitus.
    Science. 2007 Nov 2;318(5851):806-9 PMID: 17975067
  20. The incidence of gestational diabetes.
    Obstet Gynecol. 1977 Apr;49(4):497-8 PMID: 857215
  21. Frequency of diabetes mellitus in mothers of probands with gestational diabetes: possible maternal influence on the predisposition to gestational diabetes.
    Am J Obstet Gynecol. 1985 Feb 15;151(4):471-5 PMID: 3976747
  22. Gestational diabetes and the incidence of type 2 diabetes: a systematic review.
    Diabetes Care. 2002 Oct;25(10):1862-8 PMID: 12351492
  23. Gestational diabetes mellitus.
    J Clin Invest. 2005 Mar;115(3):485-91 PMID: 15765129
  24. Genomewide association analysis of coronary artery disease.
    N Engl J Med. 2007 Aug 2;357(5):443-53 PMID: 17634449
  25. Genetic polymorphisms in peroxisome proliferator-activated receptor gamma are associated with Type 2 diabetes mellitus and obesity in the Korean population.
    Diabet Med. 2005 Sep;22(9):1161-6 PMID: 16108843
  26. A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus.
    Diabetologia. 2007 May;50(5):972-9 PMID: 17342473
  27. Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population.
    Diabetologia. 2007 Dec;50(12):2461-6 PMID: 17928989
  28. Transcription factor 7-like 2 (TCF7L2) is associated with gestational diabetes mellitus and interacts with adiposity to alter insulin secretion in Mexican Americans.
    Diabetes. 2007 May;56(5):1481-5 PMID: 17317761
  29. Summary and recommendations of the Third International Workshop-Conference on Gestational Diabetes Mellitus.
    Diabetes. 1991 Dec;40 Suppl 2:197-201 PMID: 1748259
  30. Prevalence of diabetes mellitus and impaired glucose tolerance in parents of women with gestational diabetes.
    Diabetologia. 1995 Jun;38(6):693-8 PMID: 7672491
  31. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
    Science. 2007 Jun 1;316(5829):1331-6 PMID: 17463246
  32. A common variant on chromosome 9p21 affects the risk of myocardial infarction.
    Science. 2007 Jun 8;316(5830):1491-3 PMID: 17478679
  33. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes.
    Nat Genet. 2006 Mar;38(3):320-3 PMID: 16415884
  34. Pronounced insulin resistance and inadequate beta-cell secretion characterize lean gestational diabetes during and after pregnancy.
    Diabetes Care. 1997 Nov;20(11):1717-23 PMID: 9353615
  35. CRITERIA FOR THE ORAL GLUCOSE TOLERANCE TEST IN PREGNANCY.
    Diabetes. 1964 May-Jun;13:278-85 PMID: 14166677
  36. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
    Nature. 2007 Jun 7;447(7145):661-78 PMID: 17554300
  37. p16INK4a induces an age-dependent decline in islet regenerative potential.
    Nature. 2006 Sep 28;443(7110):453-7 PMID: 16957737
  38. The genetics of gestational diabetes mellitus: evidence for relationship with type 2 diabetes mellitus.
    Genet Med. 2008 Apr;10(4):240-50 PMID: 18414206
  39. 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. 2008 Aug;57(8):2226-33 PMID: 18469204
  40. Trp64Arg polymorphism of the beta3-adrenergic receptor gene in pregnancy: association with mild gestational diabetes mellitus.
    J Clin Endocrinol Metab. 1999 May;84(5):1695-9 PMID: 10323402
  41. A genome-wide association study identifies novel risk loci for type 2 diabetes.
    Nature. 2007 Feb 22;445(7130):881-5 PMID: 17293876
  42. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.
    Diabetologia. 1985 Jul;28(7):412-9 PMID: 3899825
  43. Gestational diabetes mellitus.
    JAMA. 2001 Nov 28;286(20):2516-8 PMID: 11722247
  44. Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia.
    Nat Genet. 1999 May;22(1):44-52 PMID: 10319860
  45. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.
    Nat Genet. 2007 Jun;39(6):770-5 PMID: 17460697
  46. Inhibition of cyclin-dependent kinase 5 activity protects pancreatic beta cells from glucotoxicity.
    J Biol Chem. 2006 Sep 29;281(39):28858-64 PMID: 16887799
  47. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.
    Science. 2007 Jun 1;316(5829):1336-41 PMID: 17463249
Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
1432-0428
DOI
10.1007/s00125-008-1196-4
Published
2009-02-00
Epub
2008-00-11
Pages
253-61
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
External Links
PubMed source DOI: 10.1007/s00125-008-1196-4 View journal details
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