Skip to main content

Advertisement

Log in

The role of the PPARG (Pro12Ala) common genetic variant on type 2 diabetes mellitus risk

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

Abstract

Background

Type 2 diabetes (T2DM) prevalence has been rapidly increasing in the last decades. T2DM pathogenesis is related to insulin resistance and beta-cell dysfunction. Peroxisome proliferator-activated receptor gamma (PPARG) is concerned about T2DM risk through the involvement in adipocyte differentiation and energy homeostasis. The present study aimed to find the risk associated with a common genetic variant (Pro12Ala) of the PPARG gene in the development of T2DM in a group of the Iranian population.

Methods

Totally, 149 patients with T2DM and 96 healthy individuals were recruited in this case–control study. The genotyping of the genetic variant was carried out using the polymerase chain reaction (PCR) followed by Sanger sequencing.

Results

No significant difference is observed between the CG and GG genotypes frequency of the PPARG variant (P = 0.17) in T2DM patient and the control groups. Furthermore, the frequency of the G allele was similar between case and control groups. The Pro12Ala variant may decrease the risk of diabetic retinopathy (DR) which was not statistically significant. Furthermore, the Pro12Ala variant caused a 27% increase in the risk of diabetes nephropathy (DN) among patients with T2DM but was not significant.

Conclusions

Our findings showed that the PPARG variant could not impact on T2DM development and its complications.

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

Data availability

Data from this project will be available to share.

Abbreviations

T2DM:

Type 2 diabetes mellitus

PPARs:

Peroxisome proliferator-activated receptors

PPARG:

Peroxisome proliferator-activated receptor gamma

ADA:

American diabetes association

FPG:

Fasting plasma glucose

DR:

Diabetic retinopathy

DN:

Diabetic nephropathy

HbA1c:

Hemoglobin A1c

SNP:

Single nocleutide polymorphism

PCR:

Polymerase chain reaction

χ2:

Chi-squared test

HWE:

Hardy–weinberg equilibrium

SD:

Standard deviation

BMI:

Body mass index

References

  1. Cho N, Shaw J, Karuranga S, Huang Y, da Rocha FJ, Ohlrogge A, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271–81.

    Article  CAS  Google Scholar 

  2. DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, et al. Type 2 diabetes mellitus. Nat Rev Dis Primers. 2015;1:1–22.

    Article  Google Scholar 

  3. Udler MS. Type 2 diabetes: multiple genes, multiple diseases. Curr Diab Rep. 2019;19:55.

    Article  Google Scholar 

  4. Mahajan A, Taliun D, Thurner M, Robertson NR, Torres JM, Rayner NW, et al. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat Genet. 2018;50:1505–13.

    Article  CAS  Google Scholar 

  5. Ringel J, Engeli S, Distler A, Sharma AM. Pro12Ala missense mutation of the peroxisome proliferator activated receptor γ and diabetes mellitus. Biochem Biophys Res Commun. 1999;254:450–3.

    Article  CAS  Google Scholar 

  6. Bermúdez V, Finol F, Parra N, Parra M, Pérez A, Peñaranda L, et al. PPAR-γ agonists and their role in type 2 diabetes mellitus management. Am J Ther. 2010;17:274–83.

    Article  Google Scholar 

  7. Yen C-J, Beamer BA, Negri C, Silver K, Brown KA, Yarnall DP, et al. Molecular scanning of the human peroxisome proliferator activated receptor γ (hPPARγ) gene in diabetic Caucasians: identification of a Pro12Ala PPARγ2 missense mutation. Biochem Biophys Res Commun. 1997;241:270–4.

    Article  CAS  Google Scholar 

  8. Sarhangi N, Sharifi F, Hashemian L, Doabsari MH, Heshmatzad K, Rahbaran M, et al. PPARG (Pro12Ala) genetic variant and risk of T2DM: a systematic review and meta-analysis. Sci Rep. 2020;10:1–18.

    Article  Google Scholar 

  9. Stumvoll M, Häring H. The peroxisome proliferator-activated receptor-γ2 Pro12Ala polymorphism. Diabetes. 2002;51:2341–7.

    Article  CAS  Google Scholar 

  10. Majid M, Masood A, Kadla SA, Hameed I, Ganai BA. Association of Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma 2 (PPARγ2) gene with type 2 diabetes mellitus in ethnic Kashmiri population. Biochem Genet. 2017;55:10–21.

    Article  CAS  Google Scholar 

  11. Lv X, Zhang L, Sun J, Cai Z, Gu Q, Zhang R, et al. Interaction between peroxisome proliferator-activated receptor gamma polymorphism and obesity on type 2 diabetes in a Chinese Han population. Diabetol Metab Syndr. 2017;9:1–6.

    Article  Google Scholar 

  12. Saleh R, Zahid ZI, Rahman MA, Jain P, Alam A, Kawaichi M, et al. Prevalence of PPAR-γ2 (rs1801282), RETN (rs3745367) and ADIPOQ (rs2241766) SNP markers in the Bangladeshi type 2 diabetic population. Meta Gene. 2016;10:100–7.

    Article  Google Scholar 

  13. Phani NM, Vohra M, Rajesh S, Adhikari P, Nagri SK, D’Souza SC, et al. Implications of critical PPARγ2, ADIPOQ and FTO gene polymorphisms in type 2 diabetes and obesity-mediated susceptibility to type 2 diabetes in an Indian population. Mol Genet Genom. 2016;291:193–204.

    Article  CAS  Google Scholar 

  14. Paramasivam D, Safi SZ, Qvist R, Abidin IBZ, Hairi NNM, Chinna K. Role of PPARG (Pro12Ala) in Malaysian type 2 diabetes mellitus patients. Int J Diabetes Dev Ctries. 2016;36:449–56.

    Article  CAS  Google Scholar 

  15. Mato EPM, Pokam-Fosso PE, Atogho-Tiedeu B, Noubiap JJN, Evehe M-S, Djokam-Dadjeu R, et al. The Pro12Ala polymorphism in the PPAR-γ2 gene is not associated to obesity and type 2 diabetes mellitus in a Cameroonian population. BMC Obes. 2016;3:26.

    Article  Google Scholar 

  16. Avzaletdinova DS, Sharipova L, Kochetova O, Morugova T, Erdman V, Mustafina O. Association of variable rs1801282 locus of PPARG2 gene with diabetic nephropathy. Russ J Genet. 2016;52:877–81.

    Article  CAS  Google Scholar 

  17. Gragnoli C, Cronsell J. PPARγ P12A variant in Type 2 Diabetes in Italians. Obes Metab. 2007;3:1.

    Google Scholar 

  18. Šrámková D, Kunešová M, Hainer V, Hill M, Vcelák J, Bendlová B. Is a Pro12Ala polymorphism of the PPARγ2 gene related to obesity and type 2 diabetes mellitus in the Czech population? Ann N Y Acad Sci. 2002;967:265–73.

    Article  Google Scholar 

  19. Meirhaeghe A, Fajas L, Helbecque N, Cottel D, Auwerx J, Deeb S, et al. Impact of the peroxisome proliferator activated receptor γ2 Pro12Ala polymorphism on adiposity, lipids and non-insulin-dependent diabetes mellitus. Int J Obes. 2000;24:195–9.

    Article  CAS  Google Scholar 

  20. Chistiakov DA, Potapov VA, Khodirev DS, Shamkhalova MS, Shestakova MV, Nosikov VV. The PPARγ Pro12Ala variant is associated with insulin sensitivity in Russian normoglycaemic and type 2 diabetic subjects. Diabetes Vasc Dis Res. 2010;7:56–62.

    Article  Google Scholar 

  21. Association AD. Standards of medical care in diabetes—2017 abridged for primary care providers. Clin Diab. 2017;35:5.

    Article  Google Scholar 

  22. Miller S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.

    Article  CAS  Google Scholar 

  23. Tam V, Patel N, Turcotte M, Bossé Y, Paré G, Meyre D. Benefits and limitations of genome-wide association studies. Nat Rev Genet. 2019;20:467–84.

    Article  CAS  Google Scholar 

  24. Zhu L, Huang Q, Xie Z, Kang M, Ding H, Chen B, et al. PPARGC1A rs3736265 G> A polymorphism is associated with decreased risk of type 2 diabetes mellitus and fasting plasma glucose level. Oncotarget. 2017;8:37308.

    Article  Google Scholar 

  25. Bener A, Zirie M, Al-Hamaq A, Nawaz Z, Samson N, Mohammad R. Impact of the Pro12Ala polymorphism of the PPARγ2 gene on diabetes and obesity in a highly consanguineous population. Indian J Endocrinol Metab. 2015;19:77.

    Article  CAS  Google Scholar 

  26. Kommoju UJ, Maruda J, Kadarkarai Samy S, Irgam K, Kotla JP, Reddy BM. Association of IRS1, CAPN10, and PPARG gene polymorphisms with type 2 diabetes mellitus in the high-risk population of Hyderabad. India J Diabetes. 2014;6:564–73.

    Article  CAS  Google Scholar 

  27. Chauhan G, Spurgeon CJ, Tabassum R, Bhaskar S, Kulkarni SR, Mahajan A, et al. 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. 2010;59:2068–74.

    Article  CAS  Google Scholar 

  28. Wang X, Liu J, Ouyang Y, Fang M, Gao H, Liu L. The association between the Pro12Ala variant in the PPARγ2 gene and type 2 diabetes mellitus and obesity in a Chinese population. PLoS One. 2013;8:e71985.

  29. Li J, Niu X, Li J, Wang Q. Association of PPARG Gene Polymorphisms Pro12Ala with Type 2 Diabetes Mellitus: A Meta-analysis. Curr Diabetes Rev. 2019;15:277–83.

    Article  Google Scholar 

  30. Lapice E, Monticelli A, Cocozza S, Pinelli M, Cocozza S, Bruzzese D, et al. The PPARγ2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes. J Transl Med. 2015;13:1–6.

    Article  CAS  Google Scholar 

  31. Zhang H, Zhu S, Chen J, Tang Y, Hu H, Mohan V, et al. Peroxisome proliferator–activated receptor γ polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes: evidence from meta-analysis of 18 studies. Diabetes Care. 2012;35:1388–93.

    Article  CAS  Google Scholar 

  32. Tariq K, Malik SB, Ali SHB, Maqsood SE, Azam A, Muslim I, et al. Association of Pro12Ala polymorphism in peroxisome proliferator activated receptor gamma with proliferative diabetic retinopathy. Mol Vis. 2013;19:710.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Liu L, Zheng T, Wang F, Wang N, Song Y, Li M, et al. Pro12Ala polymorphism in the PPARG gene contributes to the development of diabetic nephropathy in Chinese type 2 diabetic patients. Diabetes Care. 2010;33:144–9.

    Article  CAS  Google Scholar 

  34. Zhang Y, Meng N, Lv Z, Li H, Qu Y. The gene polymorphisms of UCP 1 but not PPAR γ and TCF 7L2 are associated with diabetic retinopathy in Chinese type 2 diabetes mellitus cases. Acta Ophthalmol. 2015;93:e223–9.

    Article  CAS  Google Scholar 

  35. Lapice E, Cocozza S, Riccardi G, Vaccaro O. Comment on: Zhang et al. Peroxisome Proliferator–Activated Receptor γ Polymorphism Pro12Ala Is Associated With Nephropathy in Type 2 Diabetes: Evidence From Meta-Analysis of 18 Studies. Diabetes Care 2012; 35: 1388–1393. Diabetes Care. 2013;36:e18-e.

Download references

Acknowledgements

The authors would like to thank all participants who involved in this project.

Author information

Authors and Affiliations

Authors

Contributions

MH managed the project and provided guidance to the research; LH and NS drafted the manuscript and performed lab genotyping; MA performed the statistical analysis; HRAM: provided clinical guidance to the research.

All authors contributed to and approved the final version of the manuscript.

Corresponding author

Correspondence to Mandana Hasanzad.

Ethics declarations

Consent for publication

Written informed consent was obtained from all the subjects and the present study was approved by ethical committee by the ethics code of IR.IAU.TMU.REC.1395.110.

Competing of interest

The authors declare that there is no conflict of interest.

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

Hashemian, L., Sarhangi, N., Afshari, M. et al. The role of the PPARG (Pro12Ala) common genetic variant on type 2 diabetes mellitus risk. J Diabetes Metab Disord 20, 1385–1390 (2021). https://doi.org/10.1007/s40200-021-00872-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-021-00872-6

Keywords

Navigation