Yonsei Med J.  2013 Mar;54(2):352-357. 10.3349/ymj.2013.54.2.352.

Association of Variants in PPARgamma2, IGF2BP2, and KCNQ1 with a Susceptibility to Gestational Diabetes Mellitus in a Korean Population

Affiliations
  • 1Department of Obstetrics & Gynecology, Gil Hospital, Graduate School of Medicine, Gachon University of Medicine and Science, Incheon, Korea. ksyob@gilhospital.com
  • 2Division of Biological Science, Gil Hospital, Graduate School of Medicine, Gachon University of Medicine and Science, Incheon, Korea.
  • 3Lab of Immunology, Gil Hospital, Graduate School of Medicine, Gachon University of Medicine and Science, Incheon, Korea.

Abstract

PURPOSE
Patients with gestational diabetes mellitus (GDM) have been reported to exhibit the same genetic susceptibility as that observed in those with type 2 diabetes mellitus (T2DM). Recent polymorphism studies have shown that several genes are related to T2DM and GDM. The aim of this study was to examine whether certain candidate genes, previously shown to be associated with T2DM, also offer a specific genetic predisposition to GDM.
MATERIALS AND METHODS
The current study was conducted in 136 Korean pregnant women, who gave birth at Gil Hospital, from October 2008 to May 2011. These study subjects included 95 subjects with GDM and 41 non-diabetic controls. We selected the specific genes of PPARgamma2, IGF2BP2, and KCNQ1 for study and amplified them using the polymerase chain reaction. This was followed by genotyping for single nucleotide polymorphisms. We then compared the genotype frequencies between patients with GDM and non-diabetic controls using the chi2 test. We obtained and analyzed clinical information using Student's t-test, and statistical analyses were conducted using logistic regression with SPSS Statistics software, version 19.0.
RESULTS
Significant differences were observed in maternal age, body mass index, weight gain and weight at time of delivery between the groups compared. Among pregnant women, polymorphisms in PPARgamma2 and IGF2BP2 were shown to be highly correlated with GDM occurrence, whereas no correlation was found for KCNQ1 polymorphisms.
CONCLUSION
Our results indicated that genetic polymorphisms could also be of value in predicting the occurrence and diagnosis of GDM.

Keyword

Gestational diabetes mellitus; type 2 diabetes mellitus; gene; single nucleotide polymorphism

MeSH Terms

Diabetes, Gestational/*genetics
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Humans
KCNQ1 Potassium Channel/*genetics
Logistic Models
PPAR gamma/*genetics
Polymorphism, Single Nucleotide
Pregnancy
RNA-Binding Proteins/*genetics
Republic of Korea
KCNQ1 Potassium Channel
PPAR gamma
RNA-Binding Proteins

Figure

  • Fig. 1 Analysis of each gene sequence (A) PPARγ2, (B) IGF2BP2, (C) KCNQ1. PPARγ2 and IGF2BP2 were interpreted in a forward manner whereas KCNQ1 was interpreted in a reverse manner.


Reference

1. Buchanan TA, Xiang AH. Gestational diabetes mellitus. J Clin Invest. 2005. 115:485–491.
Article
2. Feig DS, Palda VA. Type 2 diabetes in pregnancy: a growing concern. Lancet. 2002. 359:1690–1692.
Article
3. McLellan JA, Barrow BA, Levy JC, Hammersley MS, Hattersley AT, Gillmer MD, et al. Prevalence of diabetes mellitus and impaired glucose tolerance in parents of women with gestational diabetes. Diabetologia. 1995. 38:693–698.
Article
4. Martin AO, Simpson JL, Ober C, Freinkel N. 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. 151:471–475.
Article
5. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007. 447:661–678.
6. Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research. Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science. 2007. 316:1331–1336.
Article
7. Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007. 316:1341–1345.
Article
8. Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007. 445:881–885.
Article
9. Zeggini E, Wäedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007. 316:1336–1341.
Article
10. Stumvoll M, Häring H. The peroxisome proliferator-activated receptor-gamma2 Pro12Ala polymorphism. Diabetes. 2002. 51:2341–2347.
11. Nielsen J, Christiansen J, Lykke-Andersen J, Johnsen AH, Wewer UM, Nielsen FC. A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Mol Cell Biol. 1999. 19:1262–1270.
Article
12. Unoki H, Takahashi A, Kawaguchi T, Hara K, Horikoshi M, Andersen G, et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet. 2008. 40:1098–1102.
Article
13. Cho YM, Kim TH, Lim S, Choi SH, Shin HD, Lee HK, et al. 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. 2009. 52:253–261.
Article
14. Leary J, Pettitt DJ, Jovanovic L. Gestational diabetes guidelines in a HAPO world. Best Pract Res Clin Endocrinol Metab. 2010. 24:673–685.
Article
15. Landon MB, Mele L, Spong CY, Carpenter MW, Ramin SM, Casey B, et al. The relationship between maternal glycemia and perinatal outcome. Obstet Gynecol. 2011. 117(2 Pt 1):218–224.
Article
16. Braissant O, Foufelle F, Scotto C, Dauça M, Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology. 1996. 137:354–366.
Article
17. Shaat N, Ekelund M, Lernmark A, Ivarsson S, Almgren P, Berntorp K, et al. Association of the E23K polymorphism in the KCNJ11 gene with gestational diabetes mellitus. Diabetologia. 2005. 48:2544–2551.
Article
18. Christiansen J, Kolte AM, Hansen TO, Nielsen FC. IGF2 mRNA-binding protein 2: biological function and putative role in type 2 diabetes. J Mol Endocrinol. 2009. 43:187–195.
Article
19. Hu C, Wang C, Zhang R, Ma X, Wang J, Lu J, et al. Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population. Diabetologia. 2009. 52:1322–1325.
Article
20. Yasuda K, Miyake K, Horikawa Y, Hara K, Osawa H, Furuta H, et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet. 2008. 40:1092–1097.
Article
21. Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J, et al. A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nat Genet. 1997. 15:186–189.
Article
Full Text Links
  • YMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr