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Abstract
Gestational diabetes mellitus (GDM) is defined as abnormal glucose tolerance diagnosed for the first time during pregnancy. The pathogenesis of GDM is characterized by relatively reduced insulin secretion insufficient to meet the increased insulin demand, which is quite similar to that of type 2 diabetes mellitus. Thus GDM is considered to have a common genetic background as type 2 diabetes mellitus. However, only limited information is available for the genetic basis of GDM. In this review article, we will briefly discuss the definition, epidemiologic features, and pathophysiology of GDM. In addition, we will present the data of two recent genetic association studies regarding GDM. Most of the previously proven type 2 diabetes associated single nucleotide polymorphisms were also associated with the risk of GDM. Rapidly increasing knowledge in genetics of GDM will provide us with new insights into the pathophysiology, treatment, and prevention of GDM.
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References
1. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2009. 32:Suppl 1. 62–67.
2. Jovanovic L, Pettitt DJ. Gestational diabetes mellitus. JAMA. 2001. 286:2516–2518.
3. Buchanan TA, Xiang AH. Gestational diabetes mellitus. J Clin Invest. 2005. 115:485–491.
4. Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care. 2002. 25:1862–1868.
5. Zaidi FK, Wareham NJ, McCarthy MI, Holdstock J, Kalloo-Hosein H, Krook A, Swinn RA, O'Rahilly S. 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. 14:228–234.
6. Shaat N, Karlsson E, Lernmark A, Ivarsson S, Lynch K, Parikh H, Almgren P, Berntorp K, Groop L. Common variants in MODY genes increase the risk of gestational diabetes mellitus. Diabetologia. 2006. 49:1545–1551.
7. Shaat N, Ekelund M, Lernmark A, Ivarsson S, Almgren P, Berntorp K, Groop L. Association of the E23K polymorphism in the KCNJ11 gene with gestational diabetes mellitus. Diabetologia. 2005. 48:2544–2551.
8. Prokopenko I, McCarthy MI, Lindgren CM. Type 2 diabetes: new genes, new understanding. Trends Genet. 2008. 24:613–621.
9. Cho YM, Kim TH, Lim S, Choi SH, Shin HD, Lee HK, Park KS, Jang HC. 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.
10. Lauenborg J, Grarup N, Damm P, Borch-Johnsen K, Jorgensen T, Pedersen O, Hansen T. Common type 2 diabetes risk gene variants associate with gestational diabetes. J Clin Endocrinol Metab. 2009. 94:145–150.
12. Jang HC, Cho NH, Jung KB, Oh KS, Dooley SL, Metzger BE. Screening for gestational diabetes mellitus in Korea. Int J Gynaecol Obstet. 1995. 51:115–122.
13. Lapolla A, Dalfra MG, Fedele D. Insulin therapy in pregnancy complicated by diabetes: are insulin analogs a new tool? Diabetes Metab Res Rev. 2005. 21:241–252.
14. Buchanan TA. Pancreatic B-cell defects in gestational diabetes: implications for the pathogenesis, prevention of type 2 diabetes. J Clin Endocrinol Metab. 2001. 86:989–993.
15. Catalano PM, Tyzbir ED, Roman NM, Amini SB, Sims EA. Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women. Am J Obstet Gynecol. 1991. 165:1667–1672.
16. Van Assche FA, Aerts L, De Prins F. A morphological study of the endocrine pancreas in human pregnancy. Br J Obstet Gynaecol. 1978. 85:818–820.
17. Ward WK, Johnston CL, Beard JC, Benedetti TJ, Halter JB, Porte D Jr. Insulin resistance and impaired insulin secretion in subjects with histories of gestational diabetes mellitus. Diabetes. 1985. 34:861–869.
18. Watanabe RM, Black MH, Xiang AH, Allayee H, Lawrence JM, Buchanan TA. Genetics of gestational diabetes mellitus and type 2 diabetes. Diabetes Care. 2007. 30:Suppl 2. 134–140.
19. Retnakaran R, Connelly PW, Sermer M, Zinman B, Hanley AJ. The impact of family history of diabetes on risk factors for gestational diabetes. Clin Endocrinol (Oxf). 2007. 67:754–760.
20. Shaat N, Lernmark A, Karlsson E, Ivarsson S, Parikh H, Berntorp K, Groop L. A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus. Diabetologia. 2007. 50:972–979.
21. Leipold H, Knoefler M, Gruber C, Klein K, Haslinger P, Worda C. Plasminogen activator inhibitor 1 gene polymorphism and gestational diabetes mellitus. Obstet Gynecol. 2006. 107:651–656.
22. Alevizaki M, Thalassinou L, Grigorakis SI, Philippou G, Lili K, Souvatzoglou A, Anastasiou E. Study of the Trp64Arg polymorphism of the beta3-adrenergic receptor in Greek women with gestational diabetes. Diabetes Care. 2000. 23:1079–1083.
23. Ng MC, Park KS, Oh B, Tam CH, Cho YM, Shin HD, Lam VK, Ma RC, So WY, Cho YS, Kim HL, Lee HK, Chan JC, Cho NH. 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. 57:2226–2233.
24. Ubeda M, Rukstalis JM, Habener JF. Inhibition of cyclin-dependent kinase 5 activity protects pancreatic beta cells from glucotoxicity. J Biol Chem. 2006. 281:28858–28864.
25. Wei FY, Nagashima K, Ohshima T, Saheki Y, Lu YF, Matsushita M, Yamada Y, Mikoshiba K, Seino Y, Matsui H, Tomizawa K. Cdk5-dependent regulation of glucose-stimulated insulin secretion. Nat Med. 2005. 11:1104–1108.
26. Pascoe L, Tura A, Patel SK, Ibrahim IM, Ferrannini E, Zeggini E, Weedon MN, Mari A, Hattersley AT, McCarthy MI, Frayling TM, Walker M. Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function. Diabetes. 2007. 56:3101–3104.
27. Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, Timpson NJ, Perry JR, Rayner NW, Freathy RM, Barrett JC, Shields B, Morris AP, Ellard S, Groves CJ, Harries LW, Marchini JL, Owen KR, Knight B, Cardon LR, Walker M, Hitman GA, Morris AD, Doney AS, McCarthy MI, Hattersley AT. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007. 316:1336–1341.
28. Krishnamurthy J, Ramsey MR, Ligon KL, Torrice C, Koh A, Bonner-Weir S, Sharpless NE. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature. 2006. 443:453–457.
29. Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE, Barrett JH, Konig IR, Stevens SE, Szymczak S, Tregouet DA, Iles MM, Pahlke F, Pollard H, Lieb W, Cambien F, Fischer M, Ouwehand W, Blankenberg S, Balmforth AJ, Baessler A, Ball SG, Strom TM, Braenne I, Gieger C, Deloukas P, Tobin MD, Ziegler A, Thompson JR, Schunkert H. Genomewide association analysis of coronary artery disease. N Engl J Med. 2007. 357:443–453.
30. Jin T, Liu L. The Wnt signaling pathway effector TCF7L2 and type 2 diabetes mellitus. Mol Endocrinol. 2008. 22:2383–2392.
31. Zeggini E, McCarthy MI. TCF7L2: the biggest story in diabetes genetics since HLA? Diabetologia. 2007. 50:1–4.
32. Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent D, Belisle A, Hadjadj S, Balkau B, Heude B, Charpentier G, Hudson TJ, Montpetit A, Pshezhetsky AV, Prentki M, Posner BI, Balding DJ, Meyre D, Polychronakos C, Froguel P. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007. 445:881–885.
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