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Association between TCF7L2 polymorphism and type 2 diabetes mellitus susceptibility: a case–control study among the Bangladeshi population

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Abstract

Background

Diabetes is a severe health burden for Bangladesh. Genetic polymorphism has been reported to be one of the major risk factors for diabetes in various studies. TCF7L2 (transcription factor 7 like 2) transcripts in the human β-cell have effects on β-cell survival, function, and Wnt signaling activation. This study aimed to evaluate the frequency and association of various polymorphisms namely TCF7L2 rs12255372 and rs7903146 among Bangladeshi patients with T2DM (Type 2 Diabetes Mellitus).

Methods

This case–control study included 300 patients with T2DM and 234 healthy individuals from two health facilities in the Chattogram Division of Bangladesh. Anthropometric measurements were assessed using a self-reported, structured, eight-item questionnaire. The polymorphisms were identified by PCR–RFLP and sequencing method.

Results

A strong association of T2DM with polymorphisms was observed, including rs12255372 (p = 0.0004) and rs7903146 (p = 0.005). It was observed that the risk genotype at rs12255372 was associated with age (p = 0.009), a family history of diabetes (p < 0.0001), and HbA1C (p < 0.0001). Furthermore, it was found that rs12255372 was substantially associated with hypertension (p = 0.03), eye problems (p = 0.01), and neurological abnormalities (p = 0.02).

Conclusion

This study postulates that TCF7L2 genetic polymorphism is associated with the risk of T2DM among the studied Bangladeshi population. The findings should be replicated through more studies with a large number of samples and in different populations.

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References

  1. Tremblay J, Hamet P (2019) Environmental and genetic contributions to diabetes. Metabolism 100S:153952. https://doi.org/10.1016/j.metabol.2019.153952

    Article  CAS  Google Scholar 

  2. DeFronzo RA et al (2015) Type 2 diabetes mellitus. Nat Rev Dis Prim 1:15019. https://doi.org/10.1038/nrdp.2015.19

    Article  Google Scholar 

  3. Itariu BK, Stulnig TM (2014) Autoimmune aspects of type 2 diabetes mellitus - a mini-review. Gerontology 60(3):189–196. https://doi.org/10.1159/000356747

    Article  CAS  Google Scholar 

  4. Field SF, Howson JMM, Smyth DJ, Walker NM, Dunger DB, Todd JA (2007) Analysis of the type 2 diabetes gene, TCF7L2, in 13,795 type 1 diabetes cases and control subjects. Diabetologia 50(1):212–213. https://doi.org/10.1007/s00125-006-0506-y

    Article  CAS  Google Scholar 

  5. Galicia-Garcia U et al (2020) Pathophysiology of type 2 diabetes mellitus. Int JMol Sci. https://doi.org/10.3390/ijms21176275

    Article  Google Scholar 

  6. Akter S, Rahman MM, Abe SK, Sultana P (2014) Prevalence of diabetes and prediabetes and their risk factors among Bangladeshi adults: a nationwide survey. Bull World Health Organ 92(3):204–213. https://doi.org/10.2471/BLT.13.128371

    Article  Google Scholar 

  7. Sladek R et al (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445(7130):881–885. https://doi.org/10.1038/nature05616

    Article  CAS  Google Scholar 

  8. Xiong X, Shao W, Jin T (2012) New insight into the mechanisms underlying the function of the incretin hormone glucagon-like peptide-1 in pancreatic β-cells: the involvement of the Wnt signaling pathway effector β-catenin. Islets 4(6):359–365. https://doi.org/10.4161/isl.23345

    Article  Google Scholar 

  9. Lyssenko V et al (2007) Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest 117(8):2155–2163. https://doi.org/10.1172/JCI30706

    Article  CAS  Google Scholar 

  10. Cauchi S et al (2007) TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis. J Mol Med (Berl) 85(7):777–782. https://doi.org/10.1007/s00109-007-0203-4

    Article  CAS  Google Scholar 

  11. Chandak GR et al (2007) Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population. Diabetologia 50(1):63–67. https://doi.org/10.1007/s00125-006-0502-2

    Article  CAS  Google Scholar 

  12. Chauhan G et al (2010) Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians. Diabetes 59(8):2068–2074. https://doi.org/10.2337/db09-1386

    Article  CAS  Google Scholar 

  13. Scott LJ et al (2006) Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample. Diabetes 55(9):2649–2653. https://doi.org/10.2337/db06-0341

    Article  CAS  Google Scholar 

  14. Zhang C et al (2006) 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 55(9):2645–2648. https://doi.org/10.2337/db06-0643

    Article  CAS  Google Scholar 

  15. Anjum N, Jehangir A, Liu Y (2018) Two TCF7L2 variants associated with type 2 diabetes in the Han nationality residents of China. J Coll Physicians Surg Pak 28(10):794–797

    Google Scholar 

  16. Marquezine GF, Pereira AC, Sousa AGP, Mill JG, Hueb WA, Krieger JE (2008) TCF7L2 variant genotypes and type 2 diabetes risk in Brazil: significant association, but not a significant tool for risk stratification in the general population. BMC Med Genet 9:106. https://doi.org/10.1186/1471-2350-9-106

    Article  CAS  Google Scholar 

  17. Hayashi T, Iwamoto Y, Kaku K, Hirose H, Maeda S (2007) Replication study for the association of TCF7L2 with susceptibility to type 2 diabetes in a Japanese population. Diabetologia 50(5):980–984. https://doi.org/10.1007/s00125-007-0618-z

    Article  CAS  Google Scholar 

  18. Mayans S et al (2007) TCF7L2 polymorphisms are associated with type 2 diabetes in northern Sweden. Eur J Hum Genet 15(3):342–346. https://doi.org/10.1038/sj.ejhg.5201773

    Article  CAS  Google Scholar 

  19. Lehrer S, Rheinstein PH (2021) Diabetes, cigarette smoking and transcription factor 7-like 2 (Tcf7L2) in the UK Biobank cohort. Bull Acad Natl Med 205(9):1146–1150. https://doi.org/10.1016/j.banm.2021.09.001

    Article  CAS  Google Scholar 

  20. Standards of Medical Care in Diabetes-2017 abridged for primary care providers. Clin Diabetes 35(1):5–26 (2017). https://doi.org/10.2337/cd16-0067.

  21. Amoli MM et al (2010) Replication of TCF7L2 rs7903146 association with type 2 diabetes in an Iranian population. Genet Mol Biol 33(3):449–451. https://doi.org/10.1590/S1415-47572010005000056

    Article  CAS  Google Scholar 

  22. Alami FM et al (2012) Association of the TCF7L2 rs12255372 (G/T) variant with type 2 diabetes mellitus in an Iranian population. Genet Mol Biol 35(2):413–417. https://doi.org/10.1590/S1415-47572012005000029

    Article  CAS  Google Scholar 

  23. McCarthy M, Menzel S (2001) The genetics of type 2 diabetes. Br J Clin Pharmacol 51(3):195–199. https://doi.org/10.1046/j.1365-2125.2001.00346.x

    Article  CAS  Google Scholar 

  24. Rana H, Chavda P, Rathod C, Mavani M (2015) Socio-demographic and anthropometric profile of diabetic patients attending diabetes clinic in tertiary care hospital of central Gujarat.

  25. Borah M, Goswami R (2017) Sociodemographic and clinical characteristics of a diabetic population at a tertiary care center in Assam, India. J Soc Heal Diabetes 05(01):37–42. https://doi.org/10.4103/2321-0656.193997

    Article  Google Scholar 

  26. Hurst C, Thinkhamrop B, Tran HT (2015) The association between hypertension comorbidity and microvascular complications in type 2 diabetes patients: a nationwide cross-sectional study in Thailand. Diabetes Metab J 39(5):395–404. https://doi.org/10.4093/dmj.2015.39.5.395

    Article  Google Scholar 

  27. Shokouhi S, Delpisheh A, Haghani K, Mahdizadeh M, Bakhtiyari S (2014) Association of rs7903146, rs12255372, and rs290487 polymorphisms in TCF7L2 gene with type 2 diabetes in an Iranian Kurdish ethnic group. Clin Lab 60(8):1269–1276. https://doi.org/10.7754/clin.lab.2013.130809

    Article  CAS  Google Scholar 

  28. Bodhini D, Radha V, Dhar M, Narayani N, Mohan V (2007) The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians. Metabolism 56(9):1174–1178. https://doi.org/10.1016/j.metabol.2007.04.012

    Article  CAS  Google Scholar 

  29. El-Lebedy D, Ashmawy I (2016) Common variants in TCF7L2 and CDKAL1 genes and risk of type 2 diabetes mellitus in Egyptians. J Genet Eng Biotechnol 14(2):247–251. https://doi.org/10.1016/j.jgeb.2016.10.004

    Article  Google Scholar 

  30. Helgason A et al (2007) Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution. Nat Genet 39(2):218–225. https://doi.org/10.1038/ng1960

    Article  CAS  Google Scholar 

  31. Sale MM et al (2007) Variants of the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in an African-American population enriched for nephropathy. Diabetes 56(10):2638–2642. https://doi.org/10.2337/db07-0012

    Article  CAS  Google Scholar 

  32. Zhou K-C, Liu H-W, Wang C, Fu Y-J, Jin F (2019) Association of transcription factor 7-like 2 (TCF7L2) gene polymorphism with type 2 diabetes mellitus in Chinese Korean ethnicity population. Medicine (Baltimore) 98(5):e14288. https://doi.org/10.1097/MD.0000000000014288

    Article  CAS  Google Scholar 

  33. Alsmadi O et al (2008) Weak or no association of TCF7L2 variants with Type 2 diabetes risk in an Arab population. BMC Med Genet 9:72. https://doi.org/10.1186/1471-2350-9-72

    Article  CAS  Google Scholar 

  34. Tong Y et al (2009) Association between TCF7L2 gene polymorphisms and susceptibility to type 2 diabetes mellitus: a large human genome epidemiology (HuGE) review and meta-analysis. BMC Med Genet 10:15. https://doi.org/10.1186/1471-2350-10-15

    Article  CAS  Google Scholar 

  35. Timpson NJ et al (2009) Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome-wide association data. Diabetes 58(2):505–510. https://doi.org/10.2337/db08-0906

    Article  CAS  Google Scholar 

  36. Salonen JT et al (2007) Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium. Am J Hum Genet 81(2):338–345. https://doi.org/10.1086/520599

    Article  CAS  Google Scholar 

  37. Steinthorsdottir V et al (2007) A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet 39(6):770–775. https://doi.org/10.1038/ng2043

    Article  CAS  Google Scholar 

  38. Zeggini E et al (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316(5829):1336–1341. https://doi.org/10.1126/science.1142364

    Article  CAS  Google Scholar 

  39. Guewo-Fokeng M et al (2015) Contribution of the TCF7L2 rs7903146 (C/T) gene polymorphism to the susceptibility to type 2 diabetes mellitus in Cameroon. J Diabetes Metab Disord 14:26. https://doi.org/10.1186/s40200-015-0148-z

    Article  Google Scholar 

  40. Pourahmadi M, Erfanian S, Moradzadeh M, Jahromi AS (2015) Non-association between rs7903146 and rs12255372 polymorphisms in transcription factor 7-like 2 gene and type 2 diabetes mellitus in Jahrom City, Iran. Diabetes Metab J 39(6):512–517. https://doi.org/10.4093/dmj.2015.39.6.512

    Article  Google Scholar 

  41. Chang Y-C et al (2007) Association study of the genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene and type 2 diabetes in the Chinese population. Diabetes 56(10):2631–2637. https://doi.org/10.2337/db07-0421

    Article  CAS  Google Scholar 

  42. Zhang B-C, Li W-M, Zhu M-Y, Xu Y-W (2013) Association of TCF7L2 gene polymorphisms with type 2 diabetes mellitus in Han Chinese population: a meta-analysis. Gene 512(1):76–81. https://doi.org/10.1016/j.gene.2012.09.034

    Article  CAS  Google Scholar 

  43. Neto ABL et al (2021) Prevalence of IGFBP3, NOS3 and TCF7L2 polymorphisms and their association with hypertension: a population-based study with Brazilian women of African descent. BMC Res Notes 14(1):186. https://doi.org/10.1186/s13104-021-05598-5

    Article  CAS  Google Scholar 

  44. Yan Y et al (2010) The transcription factor 7-like 2 (TCF7L2) polymorphism may be associated with focal arteriolar narrowing in Caucasians with hypertension or without diabetes: the ARIC study. BMC Endocr Disord 10:9. https://doi.org/10.1186/1472-6823-10-9

    Article  CAS  Google Scholar 

  45. Campbell RK (2009) Type 2 diabetes: where we are today: an overview of disease burden, current treatments, and treatment strategies. J Am Pharm Assoc 49(1):S3–S9. https://doi.org/10.1331/JAPhA.2009.09077

    Article  Google Scholar 

  46. Egede LE, Ellis C (2010) Diabetes and depression: global perspectives. Diabetes Res Clin Pract 87(3):302–312. https://doi.org/10.1016/j.diabres.2010.01.024

    Article  Google Scholar 

  47. Mohan V, Seedat YK, Pradeepa R (2013) The rising burden of diabetes and hypertension in southeast asian and african regions: need for effective strategies for prevention and control in primary health care settings. Int J Hypertens 2013:409083. https://doi.org/10.1155/2013/409083

    Article  Google Scholar 

  48. Behl T, Kotwani A (2015) Exploring the various aspects of the pathological role of vascular endothelial growth factor (VEGF) in diabetic retinopathy. Pharmacol Res 99:137–148. https://doi.org/10.1016/j.phrs.2015.05.013

    Article  CAS  Google Scholar 

  49. Moreno A, Lozano M, Salinas P (2013) Diabetic retinopathy. Nutr Hosp 28(Suppl 2):53–56. https://doi.org/10.3305/nh.2013.28.sup2.6714

    Article  Google Scholar 

  50. Suganthalakshmi B et al (2006) Association of VEGF and eNOS gene polymorphisms in type 2 diabetic retinopathy. Mol Vis 12:336–341

    CAS  Google Scholar 

  51. Sanghera DK et al (2008) TCF7L2 polymorphisms are associated with type 2 diabetes in Khatri Sikhs from North India: genetic variation affects lipid levels. Ann Hum Genet 72(Pt 4):499–509. https://doi.org/10.1111/j.1469-1809.2008.00443.x

    Article  CAS  Google Scholar 

  52. Bodhini D et al (2017) Interaction between TCF7L2 polymorphism and dietary fat intake on high density lipoprotein cholesterol. PLoS ONE 12(11):e0188382. https://doi.org/10.1371/journal.pone.0188382

    Article  CAS  Google Scholar 

  53. Assmann TS, Duarte GCK, Rheinheimer J, Cruz LA, Canani LH, Crispim D (2014) The TCF7L2 rs7903146 (C/T) polymorphism is associated with risk to type 2 diabetes mellitus in Southern-Brazil. Arq Bras Endocrinol Metabol 58(9):918–925. https://doi.org/10.1590/0004-2730000003510

    Article  Google Scholar 

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Acknowledgements

Authors would like to thank all the volunteers of Disease Biology and Molecular Epidemiology Research group (dBme), Chittagong for their support.

Funding

This work was funded Grant from Research and publication office, University of Chittagong.

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Contributions

Conceptualization—AM; Method development – Writing—Original Draft Preparation, AS, KC and AM.; Writing—Review & Editing, MMH., FA., NAC., SRC and AM.; All authors have read and agreed to the published version of the manuscript.

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Correspondence to Adnan Mannan.

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This study was approved by the Ethical Review Committee of Chittagong Medical College Hospital (CMC/PG/2019/57).

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Salauddin, A., Chakma, K., Hasan, M.M. et al. Association between TCF7L2 polymorphism and type 2 diabetes mellitus susceptibility: a case–control study among the Bangladeshi population. Mol Biol Rep 50, 609–619 (2023). https://doi.org/10.1007/s11033-022-08081-x

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