Home LiteratureArticle Details
PMID: 18991055 Published · ppublish English Comparative Study Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population.

Journal of human genetics ·Vol. 53 ·No. 11-12 ·2008-00-00 ·Pages 991-998

Lee YH, Kang ES, Kim SH, Han SJ, Kim CH, Kim HJ, Ahn CW, Cha BS, Nam M, Nam CM, Lee HC

Abstract

According to recent genome-wide association studies, a number of single nucleotide polymorphisms (SNPs) are reported to be associated with type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate the association among the polymorphisms of SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1 and KCNQ1 and the risk of T2DM in the Korean population. This study was based on a multicenter case-control study, including 908 patients with T2DM and 502 non-diabetic controls. We genotyped rs13266634, rs1111875, rs10811661, rs4402960, rs8050136, rs734312, rs7754840 and rs2237892 and measured the body weight, body mass index and fasting plasma glucose in all patients and controls. The strongest association was found in a variant of CDKAL1 [rs7754840, odds ratio (OR) = 1.77, 95% CI = 1.50-2.10, p = 5.0 x 10(-11)]. The G allele of rs1111875 (OR = 1.43, 95% CI = 1.18-1.72, p = 1.8 x 10(-4)) in HHEX), the T allele of rs10811661 (OR = 1.47, 95% CI = 1.23-1.75, p = 2.1 x 10(-5)) in CDKN2A/B) and the C allele of rs2237892 (OR = 1.31, 95% CI = 1.10-1.56, p = 0.003) in KCNQ1 showed significant associations with T2DM. Rs13266634 (OR = 1.19, 95% CI = 1.00-1.42, p = 0.045) in SLC30A8 showed a nominal association with the risk of T2DM, whereas SNPs in IGF2BP2, FTO and WFS1 were not associated. In conclusion, we have shown that SNPs in HHEX, CDKN2A/B, CDKAL1, KCNQ1 and SLC30A8 confer a risk of T2DM in the Korean population.

MeSH Terms
Alpha-Ketoglutarate-Dependent Dioxygenase FTO Blood Glucose/metabolism Body Mass Index Case-Control Studies Cation Transport Proteins/genetics Cyclin-Dependent Kinase 5/genetics Cyclin-Dependent Kinase Inhibitor p15/genetics Cyclin-Dependent Kinase Inhibitor p16/genetics Diabetes Mellitus, Type 2/epidemiology,genetics Female Genetic Markers/genetics Genetic Predisposition to Disease Genome, Human Genome-Wide Association Study Genotype Homeodomain Proteins/genetics Humans KCNQ1 Potassium Channel/genetics Korea/epidemiology Male Membrane Proteins/genetics Middle Aged Polymorphism, Single Nucleotide/genetics Proteins/genetics RNA-Binding Proteins/genetics Transcription Factors/genetics Zinc Transporter 8 tRNA Methyltransferases
Chemicals
Blood Glucose CDKN2B protein, human Cation Transport Proteins Cyclin-Dependent Kinase Inhibitor p15 Cyclin-Dependent Kinase Inhibitor p16 Genetic Markers HHEX protein, human Homeodomain Proteins IGF2BP2 protein, human KCNQ1 Potassium Channel KCNQ1 protein, human Membrane Proteins Proteins RNA-Binding Proteins SLC30A8 protein, human Transcription Factors Zinc Transporter 8 wolframin protein Alpha-Ketoglutarate-Dependent Dioxygenase FTO FTO protein, human tRNA Methyltransferases Cyclin-Dependent Kinase 5 CDKAL1 protein, human
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Lee Yong-Ho
Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong Seodaemun-Gu, Seoul, 120-752, South Korea.
Kang Eun Seok
Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong Seodaemun-Gu, Seoul, 120-752, South Korea. | Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. | Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea.
Kim So Hun
Department of Internal Medicine, Inha University College of Medicine, Inchon, South Korea.
Han Seung Jin
Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong Seodaemun-Gu, Seoul, 120-752, South Korea.
Kim Chul Hoon
Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. | Department of Pharmacology, Yonsei University College of Medicine, Seoul, South Korea.
Kim Hyeong Jin
Department of Internal Medicine, Kwandong University College of Medicine, Gangneung, South Korea.
Ahn Chul Woo
Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong Seodaemun-Gu, Seoul, 120-752, South Korea. | Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. | Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea.
Cha Bong Soo
Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong Seodaemun-Gu, Seoul, 120-752, South Korea. | Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. | Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea.
Nam Moonsuk
Department of Internal Medicine, Inha University College of Medicine, Inchon, South Korea.
Nam Chung Mo
Department of Preventive Medicine and Public Health, Yonsei University College of Medicine, Seoul, South Korea.
Lee Hyun Chul
Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong Seodaemun-Gu, Seoul, 120-752, South Korea. [email protected]. | Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea. [email protected]. | Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea. [email protected].
References (34)
34 references, click to expand
  1. Common variants in WFS1 confer risk of type 2 diabetes.
    Nat Genet. 2007 Aug;39(8):951-3 PMID: 17603484
  2. Insulin secretion capacity in the development from normal glucose tolerance to type 2 diabetes.
    Diabetes Res Clin Pract. 2004 Dec;66 Suppl 1:S37-43 PMID: 15563978
  3. Genome-wide association studies provide new insights into type 2 diabetes aetiology.
    Nat Rev Genet. 2007 Sep;8(9):657-62 PMID: 17703236
  4. Heart induction by Wnt antagonists depends on the homeodomain transcription factor Hex.
    Genes Dev. 2005 Feb 1;19(3):387-96 PMID: 15687261
  5. 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
  6. Preventing Type 2 diabetes and the dysmetabolic syndrome in the real world: a realistic view.
    Diabet Med. 2003 Sep;20(9):693-702 PMID: 12925046
  7. 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
  8. A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2.
    Nat Genet. 1996 Jun;13(2):161-6 PMID: 8640221
  9. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
    Science. 2007 Jun 1;316(5829):1331-6 PMID: 17463246
  10. 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
  11. The regulation of INK4/ARF in cancer and aging.
    Cell. 2006 Oct 20;127(2):265-75 PMID: 17055429
  12. 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
  13. In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion.
    J Cell Sci. 2006 Oct 15;119(Pt 20):4199-206 PMID: 16984975
  14. Repression of Wnt/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development.
    Development. 2007 Jun;134(12):2207-17 PMID: 17507400
  15. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes.
    Nat Genet. 2000 Sep;26(1):76-80 PMID: 10973253
  16. Cdk5-dependent regulation of glucose-stimulated insulin secretion.
    Nat Med. 2005 Oct;11(10):1104-8 PMID: 16155576
  17. The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients--the EUGENE2 study.
    Diabetologia. 2008 May;51(5):816-20 PMID: 18324385
  18. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus.
    Nat Genet. 2008 Sep;40(9):1092-7 PMID: 18711367
  19. Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population.
    J Clin Endocrinol Metab. 2008 Jan;93(1):310-4 PMID: 17971426
  20. Analysis of novel risk loci for type 2 diabetes in a general French population: the D.E.S.I.R. study.
    J Mol Med (Berl). 2008 Mar;86(3):341-8 PMID: 18210030
  21. Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea.
    J Clin Endocrinol Metab. 2003 May;88(5):2300-8 PMID: 12727989
  22. Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population.
    Diabetes. 2008 Mar;57(3):791-5 PMID: 18162508
  23. Quantitative trait analysis of type 2 diabetes susceptibility loci identified from whole genome association studies in the Insulin Resistance Atherosclerosis Family Study.
    Diabetes. 2008 Apr;57(4):1093-100 PMID: 18252897
  24. High glucose decreases endothelial cell proliferation via the extracellular signal regulated kinase/p15(INK4b) pathway.
    Arch Biochem Biophys. 2007 Sep 1;465(1):164-71 PMID: 17597576
  25. Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function.
    Diabetes. 2007 Dec;56(12):3101-4 PMID: 17804762
  26. A polymorphism in the zinc transporter gene SLC30A8 confers resistance against posttransplantation diabetes mellitus in renal allograft recipients.
    Diabetes. 2008 Apr;57(4):1043-7 PMID: 18162509
  27. Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes.
    Diabetes. 2003 Feb;52(2):568-72 PMID: 12540637
  28. Zinc, insulin and diabetes.
    J Am Coll Nutr. 1998 Apr;17(2):109-15 PMID: 9550453
  29. A genome-wide association study identifies novel risk loci for type 2 diabetes.
    Nature. 2007 Feb 22;445(7130):881-5 PMID: 17293876
  30. A variant of the transcription factor 7-like 2 (TCF7L2) gene and the risk of posttransplantation diabetes mellitus in renal allograft recipients.
    Diabetes Care. 2008 Jan;31(1):63-8 PMID: 17934151
  31. Polymorphisms within novel risk loci for type 2 diabetes determine beta-cell function.
    PLoS One. 2007 Sep 05;2(9):e832 PMID: 17786204
  32. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.
    Nat Genet. 2007 Jun;39(6):770-5 PMID: 17460697
  33. 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
  34. 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
Journal of human genetics
Abbr.
J Hum Genet
ISSN
1434-5161
DOI
10.1007/s10038-008-0341-8
Email
[email protected]
Published
2008-00-00
Epub
2008-00-11
Pages
991-998
Language
English
Region
England
NLM ID
9808008
Subset
IM
External Links
PubMed source DOI: 10.1007/s10038-008-0341-8 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2