Skip to main content

Advertisement

Log in

Association of TCF7L2 rs7903146 Polymorphism with the Risk of Type 2 Diabetes Mellitus (T2DM) Among Kurdish Population in Erbil Province, Iraq

  • Original Research Article
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

The genetic predispositions responsible for developing type 2 diabetes mellitus (T2DM) in the Middle East are poorly understood. The rs7903146 single nucleotide polymorphism (SNP) located in transcription factor 7-like-2 (TCF7L2) gene has been recognized to have a vital role in the development of T2DM disorder. The current study is the first to have researched the possible association between TCF7L2 rs7903146 SNP and T2DM among Kurdish population in Kurdistan region of Iraq. The study included 212 participants, half of them were T2DM patients, and the other half were disease-free and normoglycemic controls. Genotyping was performed by using a high throughput cost and time effective tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra ARMS-PCR) assay. The rs7903146 genotypic frequencies for CC, CT and TT were 24.5%, 69.8%, and 5.7% in T2DM group respectively, and for the controls were 45.3%, 50.9%, and 3.8% respectively. The frequency of CT genotype was found significantly higher in the cases when compared to the controls (OR = 2.53, 95% CI 1.40–4.57, P value < 0.0019), which indicated that the genotype CT showed risk with diabetes. The T allele showed a high significant frequency in the patients compared to the controls (OR = 1.65, 95% CI 1.10–2.47, P value = 0.014). Our findings demonstrated that the T allele could be a risk factor for increasing the susceptibility of T2DM incidence among the Iraqi Kurdish population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Lyssenko V, Almgren P, Anevski D, Orho-Melander M, Sjögren M, Saloranta C, et al. Genetic prediction of future type 2 diabetes. PLoS Med. 2005;2(12):e345.

    Article  Google Scholar 

  2. Xue A, Wu Y, Zhu Z, Zhang F, Kemper KE, Zheng Z, et al. Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. Nat Commun. 2018;9(1):1–14.

    Article  Google Scholar 

  3. Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006;38(3):320–3. https://doi.org/10.1038/ng1732.

    Article  CAS  PubMed  Google Scholar 

  4. Jin T, Liu L. The Wnt signaling pathway effector TCF7L2 and type 2 diabetes mellitus. Mol Endocrinol. 2008;22(11):2383–92. https://doi.org/10.1210/me.2008-0135.

    Article  CAS  PubMed  Google Scholar 

  5. Ip W, Chiang YT, Jin T. The involvement of the wnt signaling pathway and TCF7L2 in diabetes mellitus: the current understanding, dispute, and perspective. Cell Biosci. 2012;2(1):28. https://doi.org/10.1186/2045-3701-2-28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Le Bacquer O, Kerr-Conte J, Gargani S, Delalleau N, Huyvaert M, Gmyr V, et al. TCF7L2 rs7903146 impairs islet function and morphology in non-diabetic individuals. Diabetologia. 2012;55(10):2677–81. https://doi.org/10.1007/s00125-012-2660-8.

    Article  CAS  PubMed  Google Scholar 

  7. Goyal R, Jialal I. Diabetes mellitus type 2. [Updated 2019 Dec 20]. StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2020.

    Google Scholar 

  8. Richmond W. Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin Chem. 1973;19(12):1350–6.

    Article  CAS  Google Scholar 

  9. Siedel J, Hagele EO, Ziegenhorn J, Wahlefeld AW. Reagent for the enzymatic determination of serum total cholesterol with improved lipolytic efficiency. Clin Chem. 1983;29(6):1075–80.

    Article  CAS  Google Scholar 

  10. Burstein M, Scholnick HR, Morfin R. Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res. 1970;11(6):583–95.

    Article  CAS  Google Scholar 

  11. Hatch FT. Practical methods for plasma lipoprotein analysis. Adv Lipid Res. 1968;6:1–68.

    Article  CAS  Google Scholar 

  12. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9. https://doi.org/10.1007/bf00280883.

    Article  CAS  PubMed  Google Scholar 

  13. Ye S, Dhillon S, Ke X, Collins AR, Day IN. An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Res. 2001;29(17):E88–E98. https://doi.org/10.1093/nar/29.17.e88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Al-Banna DA, Khuder SA. Disability assessment of diabetic patients in Erbil city. Zanco J Med Sci. 2015;19(1):902–9.

    Article  Google Scholar 

  15. Abuhendi N, Qush A, Naji F, Abunada H, Al Buainain R, Shi Z, et al. Genetic polymorphisms associated with type 2 diabetes in the Arab world: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2019;151:198–208.

    Article  CAS  Google Scholar 

  16. Cui R, Qi Z, Zhou L, Li Z, Li Q, Zhang J. Evaluation of serum lipid profile, body mass index, and waistline in Chinese patients with type 2 diabetes mellitus. Clin Interv Aging. 2016;11:445–52. https://doi.org/10.2147/cia.s104803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shokouhi S, Delpisheh A, Haghani K, Mahdizadeh M, Bakhtiyari S. Association of rs7903146, rs12255372, and rs290487 polymorphisms in TCF7L2 gene with type 2 diabetes in an Iranian Kurdish ethnic group. Clin Lab. 2014;60(8):1269–76.

    CAS  PubMed  Google Scholar 

  18. Song Y, Yeung E, Liu A, Vanderweele TJ, Chen L, Lu C, et al. Pancreatic beta-cell function and type 2 diabetes risk: quantify the causal effect using a Mendelian randomization approach based on meta-analyses. Hum Mol Genet. 2012;21(22):5010–8. https://doi.org/10.1093/hmg/dds339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ali S, Chopra R, Manvati S, Singh YP, Kaul N, Behura A, et al. Replication of type 2 diabetes candidate genes variations in three geographically unrelated Indian population groups. PLoS ONE. 2013;8(3):e58881.

    Article  CAS  Google Scholar 

  20. Pang DX, Smith AJ, Humphries SE. Functional analysis of TCF7L2 genetic variants associated with type 2 diabetes. Nutr Metab Cardiovasc Dis NMCD. 2013;23(6):550–6. https://doi.org/10.1016/j.numecd.2011.12.012.

    Article  CAS  PubMed  Google Scholar 

  21. Turki A, Al-Zaben GS, Mtiraoui N, Marmmuoch H, Mahjoub T, Almawi WY. Transcription factor-7-like 2 gene variants are strongly associated with type 2 diabetes in Tunisian Arab subjects. Gene. 2013;513(2):244–8.

    Article  CAS  Google Scholar 

  22. Ereqat S, Nasereddin A, Cauchi S, Azmi K, Abdeen Z, Amin R. Association of a common variant in TCF7L2 gene with type 2 diabetes mellitus in the Palestinian population. Acta Diabetol. 2010;47(1):195–8.

    Article  CAS  Google Scholar 

  23. Al-Sinani S, Woodhouse N, Al-Mamari A, Al-Shafie O, Al-Shafaee M, Al-Yahyaee S, et al. Association of gene variants with susceptibility to type 2 diabetes among Omanis. World J Diabetes. 2015;6(2):358.

    Article  Google Scholar 

  24. Barseem N, El-Samalehy M, Kasemy Z. Transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism, association with type 2 diabetes mellitus susceptibility. J Obes Weight Loss Ther. 2015;5(1):2.

    Article  Google Scholar 

  25. Ibrahim AT, Hussain A, Salih MA, Ibrahim OA, Jamieson SE, Ibrahim ME, et al. Candidate gene analysis supports a role for polymorphisms at TCF7L2 as risk factors for type 2 diabetes in Sudan. J Diabetes Metabol Disord. 2015;15:4. https://doi.org/10.1186/s40200-016-0225-y.

    Article  CAS  Google Scholar 

  26. Allahdini M, Kamalidehghan B, Akbari L, Azadfar P, Rahmani A, Ahmadipour F, et al. Prevalence of the rs7903146C>T polymorphism in TCF7L2 gene for prediction of type 2 diabetes risk among Iranians of different ethnicities. Drug Des Dev Ther. 2015;9:5835–41. https://doi.org/10.2147/dddt.s82485.

    Article  CAS  Google Scholar 

  27. Ensembl. Population genetics. Retrieved from https://asia.ensembl.org/Homo_sapiens/Variation/Population?db=core;r=10:112998090-112999090;v=rs7903146;vdb=variation;vf=26008090. 2020, p 1. Retrieved Apr 2020

  28. Acharya S, Al-Elq A, Al-Nafaie A, Muzaheed M, Al-Ali A. Type 2 diabetes mellitus susceptibility gene TCF7L2 is strongly associated with hyperglycemia in the Saudi Arabia population of the eastern province of Saudi Arabia. Eur Rev Med Pharmacol Sci. 2015;19(16):3100–6.

    CAS  PubMed  Google Scholar 

  29. Saadi H, Nagelkerke N, Carruthers SG, Benedict S, Abdulkhalek S, Reed R, et al. Association of TCF7L2 polymorphism with diabetes mellitus, metabolic syndrome, and markers of beta cell function and insulin resistance in a population-based sample of Emirati subjects. Diabetes Res Clin Pract. 2008;80(3):392–8. https://doi.org/10.1016/j.diabres.2008.01.008.

    Article  CAS  PubMed  Google Scholar 

  30. O'Beirne SL, Salit J, Rodriguez-Flores JL, Staudt MR, Abi Khalil C, Fakhro KA, et al. Correction: type 2 diabetes risk allele loci in the qatari population. PLoS ONE. 2016;11(8):e0161910. https://doi.org/10.1371/journal.pone.0161910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors are grateful and sincere to the Scientific Research Centre- Salahaddin University, Erbil for their financial assistance and to the staff of Layla Qasim Diabetic Centre for their contribution in developing this study.

Funding

General Directorate for Scientific Research, Salahaddin University- Erbil.

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization: SAM. Methodology: SAM and DAY. Formal analysis and investigation: SAM and DAY. Writing—original draft preparation: DAY. Writing—review and editing: SAM. Resources: DAY. Supervision: SAM.

Corresponding author

Correspondence to Delan Younus.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest with respect to the current study.

Ethical Approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation set by the committee of Ethical Standards of Salahaddin University, Erbil- Iraq. Informed consent for it was obtained from all participants for being included in the study.

Informed Consent

Informed Consent for it was obtained from all participants for being included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mustafa, S., Younus, D. Association of TCF7L2 rs7903146 Polymorphism with the Risk of Type 2 Diabetes Mellitus (T2DM) Among Kurdish Population in Erbil Province, Iraq. Ind J Clin Biochem 36, 312–318 (2021). https://doi.org/10.1007/s12291-020-00904-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12291-020-00904-7

Keywords

Navigation