Skip to main content

Advertisement

Log in

PPARɣ2, aldose reductase, and TCF7L2 gene polymorphisms: relation to diabetes mellitus

  • Research article
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Purpose

Diabetes mellitus (DM) is a growing global health concern. Genetic factors play a pivotal role in the development of diabetes. Therefore, the present work aimed to study the relation between peroxisome proliferator-activate receptors (PPARɣ2) (rs3856806), aldose reductase (AR) (rs759853), transcription factor 7 like 2 (TCF7L2) (rs7903146) gene polymorphism with diabetes in the Egyptian population.

Methods

The study included 260 diabetics and 120 healthy subjects. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism.

Results

Regression analysis revealed that PPARɣ2 TT, TCF7L2 TT were suggested to be independent risk predictors for T1DM and TCF7L2 TC, CC genotype were suggested to be independent protective factors against T1DM development. On the other hand, PPARɣ2 TT, AR TT genotypes were suggested to be independent risk predictors for T2DM susceptibility, and PPARɣ2 CT genotypes were suggested to be independent protective factors against T2DM development.

Conclusion

The present study revealed that PPARγ2 (rs3856806), TCF7L2 (rs7903146) and AR (rs759853) gene polymorphism may play an important role in the susceptibility of diabetes. Therefore, these polymorphisms may have a prognostic value for diabetes in the Egyptian population. Further work is required to confirm the role of these polymorphisms in diabetes.

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.

Similar content being viewed by others

References

  1. Şanlier N, Gencer F. Role of spices in the treatment of diabetes mellitus: A minireview. Trends Food Sci Technol 2020; 99: 441–449. https://doi.org/10.1016/j.tifs.2020.03.018

  2. Omar GA, Alib OSM, Ismaila AA, Mohamed GS. Transcription factor 7-like 2 rs7903146 polymorphism and therapeutic response to sulfonylureas in patients with type 2 diabetes. J Med Sci Res. 2018;1(3):168–72. https://doi.org/10.4103/JMISR.JMISR_43_18.

    Article  Google Scholar 

  3. Tan SY, Wong JLM, Sim YJ, Wong SS, Elhassan SAM, Tan SH, Lim GPL, Tay NWR, Annan NC, Bhattamisra SK, Candasamy M. Type 1 and 2 diabetes mellitus: a review on current treatment approach and gene therapy as potential intervention. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2019;13:364–72. https://doi.org/10.1016/j.dsx.2018.10.008.

    Article  Google Scholar 

  4. Karalliedde J, Gnudi L. Diabetes mellitus, a complex and heterogeneous disease, and the role of insulin resistance as a determinant of diabetic kidney disease. Nephrology Dialysis Transplantation. 2016;31(2, 1):206–13. https://doi.org/10.1093/ndt/gfu405.

    Article  CAS  Google Scholar 

  5. Hussain T, Tan B, Murtaza G, Liu G, Rahu N, Kalhoro MS, Kalhoro DH, Adebowale TO, Mazhar MU, Rehman ZU, Martínez Y, Khan SA, Yin Y. Flavonoids and type 2 diabetes: evidence of efficacy in clinical and animal studies and delivery strategies to enhance their therapeutic efficacy. Pharmacol Res. 2020;152:104629. https://doi.org/10.1016/j.phrs.2020.104629.

    Article  CAS  PubMed  Google Scholar 

  6. Gupta MK, Vadde R. Identification and characterization of differentially expressed genes in type 2 diabetes using in silico approach. Comput Biol Chem. 2019;79:24–35. https://doi.org/10.1016/j.compbiolchem.2019.01.010.

    Article  CAS  PubMed  Google Scholar 

  7. Choi C. Astaxanthin as a peroxisome proliferator-activated receptor (PPAR) modulator: its therapeutic implications marine drugs. 2019;17(242):1–12. https://doi.org/10.3390/md17040242.

  8. Torres-Espínola FJ, Altmäe S, Segura MT, Jerez A, Anjos T, Chisaguano M, López-Sabater MC, Entrala C, Alvarez JC, Agil A, Florido J, Catena A, Pérez-García M, Campoy C. Maternal PPARG Pro12Ala polymorphism is associated with infant's neurodevelopmental outcomes at 18 months of age. Early Hum Dev. 2015;91:457–62. https://doi.org/10.1016/j.earlhumdev.2015.05.001.

    Article  CAS  PubMed  Google Scholar 

  9. Saeidi S, Chamaie-Nejad F, Ebrahimi A, Najafi F, Rahimi Z, Vaisi-Raygani A, Shakiba E, Rahimi Z. PPARγ Pro12Ala and C161T polymorphisms in patients with acne vulgaris: contribution to lipid and lipoprotein profile. Advances in Medical Sciences. 2018;63(1):147–51. https://doi.org/10.1016/j.advms.2017.09.003.

    Article  PubMed  Google Scholar 

  10. Khodaeian M, Enayati S, Tabatabaei-Malazy O, Amoli MM. Association between genetic variants and diabetes mellitus in Iranian populations: a systematic review of observational studies. Journal of Diabetes Research. 2015; 2015 585917. 10.1155/2015/585917

  11. Gravand A, Foroughmand AM, Boroujeni MP. A study on the association of TCF7L2 rs11196205 (C/G) and CAPN10 rs3792267 (G/A) polymorphisms with type 2 diabetes mellitus in the South Western of Iran. The Egyptian Journal of Medical Human Genetics. 2018;19:403–7. https://doi.org/10.1016/j.ejmhg.2018.01.007.

    Article  Google Scholar 

  12. Sun J, Hong J, Sun S, Wang X, Peng Y, Zhou J, Huang Y, Li S, Chen W, Li C, Xu K, Ye W. Transcription factor 7-like 2 controls matrix degradation through nuclear factor κB signaling and is repressed by microRNA-155 in nucleus pulposus cells. Biomed Pharmacother. 2018;108:646–55. https://doi.org/10.1016/j.biopha.2018.09.076.

    Article  CAS  PubMed  Google Scholar 

  13. Gupta B, Singh SK. Association of aldose reductase gene polymorphism (C-106T) in susceptibility of diabetic peripheral neuropathy among north Indian population. J Diabetes Complicat. 2017;31:1085–9. https://doi.org/10.1016/j.jdiacomp.2017.04.011.

    Article  Google Scholar 

  14. Haghvirdizadeh P, Mohamed Z, Abdullah NA, Haghvirdizadeh P, Haerian MS, Haerian BS. KCNJ11: genetic polymorphisms and risk of diabetes mellitus. Journal of Diabetes Research. 2015; 2015: ID 908152. doi: https://doi.org/10.1155/2015/908152

  15. Van Hoek M, Dehghan A, Witteman JC, Van Duijn CM, Uitterlinden AG, Oostra BA, Albert Hofman A, Sijbrands EJG, Janssens ACJ. Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study. Diabetes. 2008;57(11):3122–8. https://doi.org/10.2337/db08-0425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bisse E, Abraham EC. New less temperature-sensitive microchromatographic method for the separation and quantitation of glycosylated hemoglobins using a non-cyanide buffer system. J Chromatogr B Biomed Sci Appl. 1985;344:81–91. https://doi.org/10.1016/S0378-4347(00)82009-5.

    Article  CAS  Google Scholar 

  17. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: third national health and nutrition examination survey. Am J Kidney Dis. 2003;41(1):1–12. https://doi.org/10.1053/ajkd.2003.50007.

    Article  PubMed  Google Scholar 

  18. Habalová V, Klimčáková L, Židzik J, Tkáč I. Rapid and cost effective genotyping method for polymorphisms in PPARG, PPARGC1 and TCF7L2 genes. Mol Cell Probes. 2009;23(1):52–4. https://doi.org/10.1016/j.mcp.2008.10.001.

    Article  CAS  PubMed  Google Scholar 

  19. Richeti F, Noronha RM, Waetge RTL, de Vasconcellos JPC, de Souza OF, Kneipp B, Assis N, Rocha MN, Calliari LEP, Longui CA, Monte O, de Melo MB. Evaluation of AC (n) and C (−106) T polymorphisms of the aldose reductase gene in Brazilian patients with DM1 and susceptibility to diabetic retinopathy. Mol Vis. 2007;13:740–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Dongxia L, Qi H, Lisong L, Jincheng G. Association of peroxisome proliferator-activated receptorgamma gene Pro12Ala and C161T polymorphisms with metabolic syndrome. Circ J. 2008;72(4):551–7. https://doi.org/10.1253/circj.72.551.

    Article  PubMed  Google Scholar 

  21. Tamarai K, Bhatti JS, Reddy PH. Molecular and cellular bases of diabetes: focus on type 2 diabetes mouse model-TallyHo. Biochim Biophys Acta (BBA) - Mol Basis Dis. 2019;1865:2276–84. https://doi.org/10.1016/j.bbadis.2019.05.004.

    Article  CAS  Google Scholar 

  22. Joensen LE, Madsen KP, Frimodt-Møller M, Tofte N, Willaing I, Lindhardt M, Rossing P. Changes in diabetes distress among people with type 2 diabetes during a risk screening programme for diabetic kidney disease–longitudinal observations of the PRIORITY study. J Diabetes Complicat. 2020;34(1):107467. https://doi.org/10.1016/j.jdiacomp.2019.107467.

    Article  Google Scholar 

  23. Sami W, Ansari T, Butt NS, Ab Hamid MR. Effect of diet on type 2 diabetes mellitus: a review. Int J Health Sci (Qassim). 2017;11(2):65–71.

    Google Scholar 

  24. Blanter M, Sork H, Tuomela S, Flodström-Tullberg M. Genetic and Environmental Interaction in Type 1 Diabetes: a Relationship Between Genetic Risk Alleles and Molecular Traits of Enterovirus Infection? Current Diabetes Reports. 2019;19(9):82. https://doi.org/10.1007/s11892-019-1192-8.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Cuschieri S. The genetic side of type 2 diabetes–a review. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2019;13(4):2503–6. https://doi.org/10.1016/j.dsx.2019.07.012.

    Article  Google Scholar 

  26. Jihan AM, Seham MA, Hamdia EA, Eman SM. Relationship between Diabetic Retinopathy and Methylenetetrahydrofolate Reductase Gene Polymorphism. Egyptian Journal of Hospital Medicine. 2017;67(2): 628–634. 10.12816/0037814

  27. Chutani A, Pande S. Correlation of serum creatinine and urea with glycemic index and duration of diabetes in type 1 and type 2 diabetes mellitus: a comparative study. National Journal of Physiology, Pharmacy and Pharmacology. 2017;7(9):914–9. https://doi.org/10.5455/njppp.2017.7.0515606052017.

    Article  CAS  Google Scholar 

  28. Elhefnawy KA, Elsayed AM. Prevalence of diabetic kidney disease in patients with type 2 diabetes mellitus. The Egyptian Journal of Internal Medicine. 2019;31(2):149–54. https://doi.org/10.4103/ejim.ejim_113_18.

    Article  Google Scholar 

  29. Zhou M, He S, Ping F, Li W, Zhu L, Cui X, Feng L, Zhao X, Zhang H, Li Y, Sun Q. Uncoupling Protein 2 and Peroxisome Proliferator-Activated Receptor γ Gene Polymorphisms in Association with Diabetes Susceptibility in Chinese Han Population with Variant Glucose Tolerance. International journal of endocrinology. 2018;2018, 1–16. 10.1155/2018/4636783

  30. Lv X, Zhang L, Sun J, Cai Z, Gu Q, Zhang R, Shan A. Interaction between peroxisome proliferator-activated receptor gamma polymorphism and obesity on type 2 diabetes in a Chinese Han population. Diabetology & Metabolic Syndrome. 2017;9(1):1–6. 10.1186/s13098-017-0205-5 PMID: 28123453

  31. Vergotine Z, Kengne AP, Erasmus RT, Yako YY, Matsha TE. Rare mutations of peroxisome proliferator-activated receptor gamma: frequencies and relationship with insulin resistance and diabetes risk in the mixed ancestry population from South Africa. International Journal of Endocrinology. 2014;2014, 1–8. 10.1155/2014/187985 PMID: 25197274.

  32. Pattanayak AK, Bankura B, Balmiki N, Das TK, Chowdhury S, Das M. Role of peroxisome proliferator-activated receptor gamma gene polymorphisms in type 2 diabetes mellitus patients of West Bengal, India. J Diabetes Investig. 2014; 5(2): 188–191.. 10.1111/jdi.12130 PMID: 24843759

  33. Ding S, Liu L, Zhuge QC, Yu Z, Zhang X, Xie J. The Meta-analysis of the association of PPARG P12A, C161T polymorphism and coronary heart disease. Wien Klin Wochenschr. 2012;124:671–7. https://doi.org/10.1007/s00508-012-0223-0.

    Article  CAS  PubMed  Google Scholar 

  34. Jiang J, Gajalakshmi V, Wang J, Kuriki K, Suzuki S, Nakamura S, Akasaka S, Ishikawa H, Tokudome S. Influence of the C161T but not Pro12Ala polymorphism in the peroxisome proliferator activated receptor gamma on colorectal cancer in an Indian population. Cancer Sci. 2005;96:507–12. https://doi.org/10.1111/j.1349-7006.2005.00072.x.

    Article  CAS  PubMed  Google Scholar 

  35. Siezen CL, van Leeuwen AI, Kram NR, Luken ME, van Kranen HJ, Kampman E. Colorectal adenoma risk is modified by the interplay between polymorphisms in arachidonic acid pathway genes and fish consumption. Carcinogenesis. 2005;26:449–57. https://doi.org/10.1093/carcin/bgh336.

    Article  CAS  PubMed  Google Scholar 

  36. Shrestha UK, Karimi O, Crusius JB, Zhou F, Wang Z, Chen Z, van Bodegraven AA, Xiao, J, Morré SA, Wang H, Li J, Xia B Distribution of peroxisome proliferator-activated receptor-gamma polymorphisms in Chinese and Dutch patients with inflammatory bowel disease inflammatory bowel disease 2009;16(2): 312–319. https://doi.org/10.1002/ibd.21059.

  37. Chang K, Shieh B, Petrash JM. Role of aldose reductase in diabetes-induced retinal microglia activation. Chem Biol Interact. 2019;302:46–52. https://doi.org/10.1016/j.cbi.2019.01.020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mansour MM, El-Hussiny MA, Ghareeb NA, Marzouk HFA, Lumon NI. Serum 8-hydroxydeoxyguanosine and aldose reductase C-106T polymorphism in type 2 diabetes mellitus and its relation to complications in Egyptian patients. Comp Clin Pathol. 2018;27(1):99–105. https://doi.org/10.1007/s00580-017-2558-4.

    Article  CAS  Google Scholar 

  39. Sivenius K, Pihlajamäki J, Partanen J, Niskanen L, Laakso M, Uusitupa M. Aldose reductase gene polymorphisms and peripheral nerve function in patients with type 2 diabetes. Diabetes Care. 2004;27(8):2021–6. https://doi.org/10.2337/diacare.27.8.2021.

    Article  CAS  PubMed  Google Scholar 

  40. Watarai A, Nakashima E, Hamada Y, Watanabe G, Naruse K, Miwa K, Kobayashi Y, Kamiya H, Nakae M, Hamajima N, Sekido Y, Niwa T, Oiso Y, Nakamura J. Aldose reductase gene is associated with diabetic macroangiopathy in Japanese type 2 diabetic patients. Diabetic Medicine. 2006;23(8): 894–899. 10.1111/j.1464-5491.2006.01946.x.

  41. Shen J, Fang Y, Ge W. Polymorphism in the transcription factor 7-like 2 (TCF7L2) gene is associated with impaired proinsulin conversion--a meta-analysis. Diabetes Res Clin Pract. 2015;109(1):117–23. https://doi.org/10.1016/j.diabres.2015.04.020.

    Article  CAS  PubMed  Google Scholar 

  42. Facchinello N, Tarifeño-Saldivia E, Grisan E, Schiavone M, Peron M, Mongera A, Ek O, Schmitner N, Meyer D, Peers B, Tiso N, Argenton F. Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration. Sci Rep. 2017;7(1):9605. https://doi.org/10.1038/s41598-017-09867-x.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Abd El Razek NY, Wissa NR, Nassar HM, Omar SA. Association of RS 7903146 (C/T) Single Nucleotide Polymorphism at Transcription Factor 7 Like 2 Gene with Type 2 Diabetes Mellitus in Egyptian Patients. Suez Canal University Medical Journal. 2016; 19(1): 29–38. 10.21608/SCUMJ.2016.43911

  44. Welter M, Frigeri HR, Souza EM, Souza ALF, Alberton D, Picheth G, Rego FGM. Polymorphisms in the Fat Mass and Obesity Associated (FTO) and Transcription factor 7-like 2 (TCF7L2) genes in Euro-Brazilian individuals with type 2 diabetes. Diabetes, Obesity & Metabolic Disorders Open Access. 2016;2: 1–6. ID: 52214790.

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

  46. Barseem NF. El- Samalehy MF, Kasemy ZA. Transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism, association with type 2 diabetes mellitus susceptibility. J Obes Weight Loss Ther. 2015;5(1):1–7. https://doi.org/10.4172/2165-7904.1000250.

    Article  Google Scholar 

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

  48. Ibrahim AT, Hussain A, Salih MA, Ibrahim OA, Jamieson SE, Ibrahim ME, Blackwell JM, Mohamed HS. Candidate gene analysis supports a role for polymorphisms at TCF7L2 as risk factors for type 2 diabetes in Sudan. Journal of Diabetes & Metabolic Disorders. 2015; 15(1): 4. 10.1186/s40200-016-0225-y.

  49. Demirsoy IH, Aras N, Cinkir U. TCF7L2 rs7903146 gene variation is associated with risk of type 2 diabetes in Turkish population. Journal of Clinical & Medical Genomics. 2016;4(2):1–3. https://doi.org/10.4172/2472-128X.1000141.

    Article  Google Scholar 

  50. Dou H, Ma E, Yin L, Jin Y, Wang H. The association between gene polymorphism of TCF7L2 and type 2 diabetes in Chinese Han population: a meta-analysis. PloS one. 2013; 8(3):e59495. 10.1371/journal.pone.0059495.

  51. Ding W, Xu L, Zhang L, Han Z, Jiang Q, Wang Z, Jin S. Meta-analysis of association between TCF7L2 polymorphism rs7903146 and type 2 diabetes mellitus. BMC Med Genet. 2018; 19 (38): 1–12. 10.1186/s12881-018-0553-5.

  52. Mandour I, Darwish R, Fayez R, Naguib M, El-Sayegh S. TCF7L2 gene polymorphisms and susceptibility to type 2 diabetes mellitus, a pilot study. Biomedical & Pharmacology Journal. 2018;11(2):1043–9. https://doi.org/10.13005/bpj/1465.

    Article  CAS  Google Scholar 

  53. Verma S, Srivastava N, Banerjee M. PS 04-25 association of tcf7l2 and ppar [gamma] gene variants with type 2 diabetes mellitus in north indian population. J Hypertens. 2016;34:e139–40. https://doi.org/10.1097/01.hjh.0000500259.57616.2a.

    Article  Google Scholar 

  54. Guewo-Fokeng M, Sobngwi E, Atogho-Tiedeu B, Donfack OS, Noubiap JJN, Ngwa EN, Mato-Mofo EP, Fosso PP, Djahmeni E, Djokam-Dadjeu R , Evehe M, Aminkeng F 5, Mbacham WF, Mbanya JC. Contribution of the TCF7L2 rs7903146 (C/T) gene polymorphism to the susceptibility to type 2 diabetes mellitus in Cameroon. Journal of Diabetes & Metabolic Disorders. 2015; 14: 1. 10.1186/s40200-015-0148-z

  55. Yousef AA, Behiry EG, Abd Allah WM, Hussien AM, Abdelmoneam AA, Imam MH, Hikal DM. IRS-1 genetic polymorphism (r. 2963G> A) in type 2 diabetes mellitus patients associated with insulin resistance. The application of clinical genetics. 2018; 11: 99–106. 10.2147/TACG.S171096.

  56. Lin S, Peng Y, Cao M, Chen R, Hu J, Pu Z, Cai Z, Mou L. Association between aldose reductase gene C (−106) T polymorphism and diabetic retinopathy: a systematic review and Meta-analysis. Ophthalmic Res. 2020;63(3):224–33. https://doi.org/10.1159/000503972.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was granted by the authors themselves. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hadeel Ahmed Shawki.

Ethics declarations

Declaration of interest

The authors declared that there is no conflict of interest. The authors alone are responsible for the content and writing of this article.

Ethical approval

This study was ethically approved by Mansoura University Ethics Committee at the Faculty of Science (Sci-ch-ph -2020-28).

Informed consent

All the authors have read the manuscript and given their consent to Participate and Publish.

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

Shawki, H.A., Abo-hashem, E.M., Youssef, M.M. et al. PPARɣ2, aldose reductase, and TCF7L2 gene polymorphisms: relation to diabetes mellitus. J Diabetes Metab Disord 21, 241–250 (2022). https://doi.org/10.1007/s40200-021-00963-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-021-00963-4

Keywords

Navigation