Association of TCF7L2 Polymorphisms with Susceptibility to Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis

Document Type : Systematic Review

Authors

1 Department of Obstetrics and Gynecology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

2 Department of Obstetrics and Gynecology, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran

3 Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

4 Department of Pediatrics, Islamic Azad University of Yazd, Yazd, Iran

5 Neonatal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

6 Hematology and Oncology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

7 Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

8 Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Abstract

Background: Gestational diabetes mellitus (GDM) is a complex metabolic disorder of pregnancy with a strong genetic predisposition. GDM is associated with complications during pregnancy and increased risk of type 2 diabetes later in mothers and develops a vicious cycle of metabolic diseases for future generations. Evidence is accumulating that women with genetic variants at transcription factor 7-like 2 (TCF7L2) gene are more susceptible to GDM. The aim of the current meta-analysis was to assess the association of the TCF7L2 polymorphisms with GDM risk.
Methods: PubMed, Web of Science, Embase, SID and CNKI databases were searched to identify relevant studies up to November 01, 2020. Using the fixed-effect or random-effect model, the pooled odds ratio and its corresponding 95% confidence interval were computed.
Results: A total of 38 case-control studies including 24 studies with 6021 cases and 13289 controls on rs7903146, eight studies with 2404 cases and 2615 controls on rs12255372 and six studies with 1357 cases and 2858 controls on rs7901695 polymorphism were selected. Pooled data showed that there was a significant association between the TCF7L2 rs7903146, rs12255372 and rs7901695 polymorphisms and an increased risk of GDM in whole population. Stratified analysis showed that the TCF7L2 rs7903146 polymorphism was associated with GDM in Caucasian, mixed and Chinese women, but not in Asians. Moreover, the TCF7L2 rs12255372 polymorphism was associated with GDM in Asians and Caucasians women with GDM.
Conclusion: The combined data indicated that the TCF7L2 rs7903146, rs12255372 and rs7901695 polymorphisms were associated with a significant risk of GDM in whole population, especially in Caucasian women.

Keywords


  1. Muche AA, Olayemi OO, Gete YK. Prevalence of gestational diabetes mellitus and associated factors among women attending antenatal care at Gondar town public health facilities, Northwest Ethiopia. BMC Pregnancy Childbirth 2019; 19(1): 334.
  2. Asadi M, Shahzeidi M, Nadjarzadeh A, Hashemi Yusefabad H, Mansoori A. The relationship between pre‐pregnancy dietary patterns adherence and risk of gestational diabetes mellitus in Iran: A case–control study. Nutr Diet 2019; 76(5): 597-603.
  3. Hunt KJ, Schuller KL. The increasing prevalence of diabetes in pregnancy. Obstet Gynecol Clin North Am 2007; 34(2): 173-99.
  4. Herring SJ, Oken E. Obesity and diabetes in mothers and their children: Can we stop the intergenerational cycle? Curr Diab Rep 2011; 11(1): 20-7.
  5. Słupecka-Ziemilska M, Wychowański P, Puzianowska-Kuznicka M. Gestational diabetes mellitus affects offspring’s epigenome. Is there a way to reduce the negative consequences? Nutrients 2020; 12(9): 2792.
  6. Zhu Z, Cao F, Li X. Epigenetic programming and fetal metabolic programming. Front Endocrinol (Lausanne) 2019; 10: 764.
  7. Franzago M, Fraticelli F, Stuppia L, Vitacolonna E. Nutrigenetics, epigenetics and gestational diabetes: consequences in mother and child. Epigenetics 2019; 14(3): 215-35.
  8. Melchior H, Kurch-Bek D, Mund M. The prevalence of gestational diabetes: a population-based analysis of a nationwide screening program. Dtsch Arztebl Int 2017; 114(24): 412-8.
  9. International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010; 33(3): 676-82.
  10. Niroomand M, Afsar J, Hosseinpanah F, Afrakhteh M, Farzaneh F, Serahati S. Comparison of the international association of diabetes in pregnancy study group criteria with the old American diabetes association criteria for diagnosis of gestational diabetes mellitus. Int J Endocrinol Metab 2019; 17(4): e88343.
  11. Moses RG, Morris GJ, Petocz P, Sangil F, Garg D. The impact of potential new diagnostic criteria on the prevalence of gestational diabetes mellitus in Australia. Med J Aust 2011; 194(7): 338-40.
  12. Yahaya TO, Salisu T, Abdulrahman YB, Umar AK. Update on the genetic and epigenetic etiology of gestational diabetes mellitus: a review. Egypt J Med Hum Genet 2020; 21(1): 1-13.
  13. Kampmann U, Knorr S, Fuglsang J, Ovesen P. Determinants of maternal insulin resistance during pregnancy: an updated overview. J Diabetes Res 2019; 2019: 5320156.
  14. de Sousa RAL, Torres YS, Figueiredo CP, Passos GF, Clarke JR. Consequences of gestational diabetes to the brain and behavior of the offspring. An Acad Bras Cienc 2018; 90(2 suppl 1): 2279-91.
  15. Nunes RD, Flôres ME, Seemann M, Traebert E, Traebert J. Two criteria of oral glucose tolerance test to diagnose gestational diabetes mellitus. Rev Assoc Med Bras (1992) 2020; 66(2): 139-45.
  16. Blum AK. Insulin use in pregnancy: An update. Diabetes Spectr 2016; 29(2): 92-7.
  17. Aktün HL, Uyan D, Yorgunlar B, Acet M. Gestational diabetes mellitus screening and outcomes. J Turk Ger Gynecol Assoc 2015; 16(1): 25-9.
  18. Xiong X, Saunders LD, Wang FL, Demianczuk NN. Gestational diabetes mellitus: Prevalence, risk factors, maternal and infant outcomes. Int J Gynaecol Obstet 2001; 75(3): 221-8.
  19. Patel M, Singh M, Sachan P, Sachan R. Outcome in gestational diabetes mellitus after various treatment modality: A tertiary center experience in North India. Ann Trop Med Public Health 2018; 11(4): 140-4.
  20. Kc K, Shakya S, Zhang H. Gestational diabetes mellitus and macrosomia: A literature review. Ann Nutr Metab 2015; 66(Suppl 2): 14-20.
  21. Mitanchez D. What neonatal complications should the pediatrician be aware of in case of maternal gestational diabetes? World J Diabetes 2015; 6(5): 734-43.
  22. Mitanchez D. Complications fœtales et néonatales du diagnostic gestationnel : mortalité périnatale, malformations congénitales, macrosomie, dystocie des épaules, traumatisme obstétrical, complications néonatales. J Gynecol Obstet Biol Reprod (Paris) 2010; 39(8 Suppl 2). [In French].
  23. Reece EA. The fetal and maternal consequences of gestational diabetes mellitus. J Matern Fetal Neonatal Med 2010; 23(3): 199-203.
  24. da Silva AL, do Amaral AR, de Oliveira DS, Martins L, Silva MR, Silva JC. Desfechos neonatais de acordo com diferentes terapêuticas do diabetes mellitus gestacional. J. Pediatr 2017; 93(1): 87-93.
  25. Garcia-Vargas L, Addison SS, Nistala R, Kurukulasuriya D, Sowers JR. Gestational diabetes and the offspring: Implications in the development of the cardiorenal metabolic syndrome in offspring. Cardiorenal Med 2012; 2(2): 134-42.
  26. Robitaille J, Grant AM. The genetics of gestational diabetes mellitus: Evidence for relationship with type 2 diabetes mellitus. Genet Med 2008; 10(4): 240-50.
  27. Pappa KI, Gazouli M, Economou K, Daskalakis G, Anastasiou E, Anagnou NP, et al. Gestational diabetes mellitus shares polymorphisms of genes associated with insulin resistance and type 2 diabetes in the Greek population. Gynecol Endocrinol 2011; 27(4): 267-72.
  28. Lowe WL, Scholtens DM, Sandler V, Hayes MG. Genetics of gestational diabetes mellitus and maternal metabolism. Curr Diab Rep 2016; 16(2): 15.
  29. Lauenborg J, Grarup N, Damm P, Borch-Johnsen K, Jørgensen T, Pedersen O, et al. Common type 2 diabetes risk gene variants associate with gestational diabetes. J Clin Endocrinol Metab 2009; 94(1): 145-50.
  30. Powe CE, Kwak SH. Genetic studies of gestational diabetes and glucose metabolism in pregnancy. Curr Diab Rep 2020; 20(12): 69.
  31. Wang B, Xue X. Investigations of associations between seven gene polymorphisms and gestational diabetes mellitus: Evidence from a meta-analysis. Gynecol Obstet Invest 2020; 85(3): 229-36.
  32. Hasan M, MA H, K N-H, Panthi S, Aktar Y, Sultana N, Jahan S, et al. TCF7L2 gene rs7903146 polymorphism is observed in gestational diabetes mellitus in Bangladesh. Integr Obesity Diabetes 2016; 2(4).
  33. Chen X, Ayala I, Shannon C, Fourcaudot M, Acharya NK, Jenkinson CP, et al. The diabetes gene and wnt pathway effector TCF7L2 regulates adipocyte development and function. Diabetes 2018; 67(4): 554-68.
  34. Vural HC. Tcf7l2 gene polymorphism in T2dm with patients in Turkish population. J Clin Epigenet 2017; 3(3): 27.
  35. Hou N, Ye B, Li X, Margulies KB, Xu H, Wang X, et al. Transcription Factor 7-like 2 Mediates Canonical Wnt/β-Catenin Signaling and c-Myc Upregulation in Heart Failure. Circ Heart Fail 2016; 9(6): 10.1161.
  36. Zhang C, Qi L, Hunter DJ, Meigs JB, Manson JE, van Dam RM, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene and the risk of type 2 diabetes in large cohorts of U.S. women and men. Diabetes 2006; 55(9): 2645-48.
  37. Zhou Y, Park SY, Su J, Bailey K, Ottosson-Laakso E, Shcherbina L, et al. TCF7L2 is a master regulator of insulin production and processing. Hum Mol Genet 2014; 23(24): 6419-31.
  38. Ekelund M, Shaat N, Almgren P, Anderberg E, Landin-Olsson M, Lyssenko V, et al. Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus. Diabetes Res Clin Pract 2012; 97(3): 394-8.
  39. Gorczyca-Siudak D, Michalak-Wojnowska M, Gorczyca T, Mosiewicz B, Kwaśniewska A, Filip A, et al. Association between rs7901695 and rs7903146 polymorphisms of the TCF7L2 gene and gestational diabetes in the population of Southern Poland. Ginekol Pol 2016; 87(11): 745-750.
  40. Moghimi M, Sobhan MR, Jarahzadeh MH, Morovati-Sharifabad M, Aghili K, Ahrar H, et al. Association of GSTM1, GSTT1, GSTM3, and GSTP1 genes polymorphisms with susceptibility to osteosarcoma: a case- control study and meta-analysis. Asian Pac J Cancer Prev 2019; 20(3): 675-82.
  41. Shaat N, Lernmark Å, Karlsson E, Ivarsson S, Parikh H, Berntorp K, et al. A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus. Diabetologia 2007; 50(5): 972-9.
  42. 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(2): 253-61.
  43. Freathy RM, Hayes MG, Urbanek M, et al. Hyperglycemia and adverse pregnancy outcome (HAPO) study: Common genetic variants in GCK and TCF7L2 are associated with fasting and postchallenge glucose levels in pregnancy and with the new consensus definition of gestational diabetes mellitus from the International Association of Diabetes and Pregnancy Study Groups. Diabetes 2010; 59(10): 2682-9.
  44. Rizk N, Abdullah Rooshenas A, Fouladi E, Abdullah Rooshenas F, Al-Ali K, Al-Khinji M, et al. The associations of transcription factor 7-like 2 [TCF7L2] gene with gestational diabetes mellitus in state of Qatar. Qatar Foundation Annual Research Forum Proceedings 2011; 2011(1): BMP8.
  45. Aris NKM, Ismai NAM, Mahdy ZA, Ahmad S, Naim NM, Siraj HH,et al. An analysis of targeted single nucleotide polymorphisms for the risk prediction of gestational diabetes mellitus in a cohort of Malaysian patients - UKM Journal Article Repository. Asia‐Pacific J Mol Med 2011; 1(1): 1-8.
  46. Papadopoulou A, Lynch KF, Shaat N, Håkansson R, Ivarsson SA, Berntorp K, et al. Gestational diabetes mellitus is associated with TCF7L2 gene polymorphisms independent of HLA-DQB1*0602 genotypes and islet cell autoantibodies. Diabet Med 2011; 28(9): 1018-27.
  47. Včelák J, Vejražková D, Vaňková M, Lukášová P, Bradnová O, Hálková T, et al. T2D risk haplotypes of the TCF7L2 gene in the Czech population sample: the association with free fatty acids composition. Physiol Res 2012; 61(3): 229-40.
  48. Ekelund M, Shaat N, Almgren P, Anderberg E, Landin-Olsson M, Lyssenko V, et al. Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus. Diabetes Res Clin Pract 2012; 97(3): 394-8.
  49. Klein K, Haslinger P, Bancher-Todesca D, Leipold H, Knöfler M, Handisurya A, et al. Transcription factor 7-like 2 gene polymorphisms and gestational diabetes mellitus. J Matern Fetal Neonatal Med 2012; 25(9): 1783-6.
  50. Pagán A, Sabater-Molina M, Olza J, Prieto-Sánchez MT, Blanco-Carnero JE, Parrilla JJ, et al. A gene variant in the transcription factor 7-like 2 (TCF7L2) is associated with an increased risk of gestational diabetes mellitus. Eur J Obstet Gynecol Reprod Biol 2014; 180(1): 77-82.
  51. Reyes-López R, Perez-Luque E, Malacara JM. Relationship of lactation, BMI, and rs12255372 TCF7L2 polymorphism on the conversion to type 2 diabetes mellitus in women with previous gestational diabetes. Gynecol Endocrinol 2019; 35(5): 412-6.
  52. Thomas N, Mahesh DM, Chapla A, Paul J, Shwetha N, Christina F, et al. Does TCF7L2 polymorphisms increase the risk of gestational diabetes mellitus in South Indian population? Endocrine Abstracts 2014; 34: P270.
  53. ZXJ H. Relationship between rs7903146‐T/C polymorphism of TCFTL2 gene and gestational diabetes mellitus. J Chin Phys 2015; 17: 65-67. [In Chinese].
  54. Shi X, Cai Q, Zou M, Shen Y. Correlation between TCF7L2 gene polymorphism and genetic susceptibility in women with gestational diabetes mellitus. Zhonghua Fu Chan Ke Za Zhi 2014; 49(8): 588-93. [In Chinese].
  55. de Melo SF, Frigeri HR, dos Santos-Weiss ICR, Réa RR, de Souza EM, Alberton D, et al. Polymorphisms in FTO and TCF7L2 genes of Euro-Brazilian women with gestational diabetes. Clin Biochem 2015; 48(16-17): 1064-7.
  56. Huerta-Chagoya A, Vázquez-Cárdenas P, Moreno-Macías H, Tapia-Maruri L, Rodríguez-Guillén R, López-Vite E, et al. Genetic determinants for gestational diabetes mellitus and related metabolic traits in Mexican women. PLoS One 2015; 10(5): e0126408.
  57. Stuebe AM, Wise A, Nguyen T, Herring A, North KE, Siega-Riz AM. Maternal genotype and gestational diabetes. Am J Perinatol 2014; 31(1): 69-76.
  58. Anghebem-Oliveira MI, Martins BR, Alberton D, de Souza Ramos EA, Picheth G, Rego FG de M. Type 2 diabetes-associated genetic variants of FTO, LEPR, PPARg, and TCF7l2 in gestational diabetes in a Brazilian population. Arch Endocrinol Metab 2017; 61(3): 238-48.
  59. Sonagra AD, Biradar SM, Dattatreya K, Jayaprakash Murthy DS. Normal pregnancy- A state of insulin resistance. J Clin Diagn Res 2014; 8(11): CC01-3.
  60. Maltepe E, Penn AA. Development, function, and pathology of the placenta. In: Gleason CA, Juul SE, editor. Avery’s diseases of the newborn. 10th London, Uk: Elsevier Inc.; 2018. p. 40-60.
  61. Napso T, Yong HEJ, Lopez-Tello J, Sferruzzi-Perri AN. The role of placental hormones in mediating maternal adaptations to support pregnancy and lactation. Front Physiol 2018; 9: 1091.
  62. Ryan EA. Hormones and insulin resistance during pregnancy. Lancet 2003; 362(9398): 1777-8.
  63. Ye D, Fei Y, Ling Q, Xu W, Zhang Z, Shu J, et al. Polymorphisms in TCF7L2 gene are associated with gestational diabetes mellitus in Chinese Han population. Sci Rep 2016; 6(1): 30686.
  64. Cropano C, Santoro N, Groop L, Man CD, Cobelli C, Galderisi A, et al. The rs7903146 variant in the tcf7l2 gene increases the risk of prediabetes/type 2 diabetes in obese adolescents by impairing b-cell function and hepatic insulin sensitivity. Diabetes Care 2017; 40(8): 1082-9.
  65. Adams JD, Vella A. What can diabetes-associated genetic variation in TCF7L2 teach us about the pathogenesis of type 2 diabetes? Metab Syndr Relat Disord 2018; 16(8): 383-9.
  66. Chang S, Wang Z, Wu L, Lu X, Shangguan S, Xin Y, et al. Association between TCF7L2 polymorphisms and gestational diabetes mellitus: A meta-analysis. J Diabetes Investig 2017; 8(4): 560-70.
  67. Lin PC, Lin WT, Yeh YH, Wung SF. Transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism as a risk factor for gestational diabetes mellitus: A meta-analysis. PLoS One 2016; 11(4): e0153044.
  68. Kang S, Xie Z, Zhang D. Association of the rs7903146 polymorphism in transcription factor 7-like 2 (TCF7L2) gene with gestational diabetes mellitus: A meta-analysis. Gynecol Endocrinol 2013; 29(10): 873-7.
Volume 4, Issue 2
December 2021
Pages 88-103
  • Receive Date: 10 February 2022
  • Accept Date: 10 February 2022
  • First Publish Date: 10 February 2022