Skip to main content
Log in

Association of common single-nucleotide polymorphism of HHEX with type 2 diabetes mellitus

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

Abstract

Background

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease that occurs as a result of insulin resistance and low insulin production. T2DM involves many organ systems that include macro-vascular and micro-vascular complications. Several genome-wide association studies (GWAS) and candidate gene studies have suggested a large number of single nucleotide polymorphisms (SNPs) on several genes such as HHEX that were associated with T2DM susceptibility. The current study aims to look at the relationship between the risk of T2DM and the HHEX gene variant rs7923837.

Methods

In this case-control study genotyping of rs7923837 of the HHEX gene was performed using the PCR-RFLP and Sanger sequencing method.

Results

Frequencies of GG genotype of rs7923837 polymorphism of HHEX among subjects with and without diabetes mellitus were 33.77% and 25.47% respectively. Corresponding prevalence for the AG genotype was 51.08% and 64.15% among subjects with and without diabetes mellitus respectively. The differences were not statistically significant (p = 0.08).

Conclusion

Our study revealed that polymorphisms rs7923837 of HHEX were not associated with T2DM.

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

This project has no associated data to be available.

Abbreviations

T2DM:

type 2 diabetes mellitus

GWAS:

genome-wide association studies

HHEX:

hematopoietically expressed homeobox

SNPs:

single nucleotide polymorphisms

FPG:

fasting plasma glucose

HbA1c:

hemoglobin A1c

OGTT:

oral glucose tolerance test

ADA:

American Diabetes Association

PCR:

polymerase chain reaction

IDF:

International Diabetes Federation

DR:

diabetic retinopathy

DN:

diabetic nephropathy

OR:

odds ratio

CI:

confidence interval

References

  1. Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119.

    Article  PubMed  Google Scholar 

  2. Chang YC, Liu PH, Yu YH, Kuo SS, Chang TJ, Jiang YD, et al. Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population: a replication study and meta-analysis. PLoS ONE. 2014;9(4):e95045.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Shojima N, Yamauchi T. Progress in genetics of type 2 diabetes and diabetic complications. J Diabetes Investig. 2023;14(4):503–15.

  4. Ali O. Genetics of type 2 diabetes. World J Diabetes. 2013;4(4):114–23.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ferrannini E, Gastaldelli A, Iozzo P. Pathophysiology of prediabetes. Med Clin North Am. 2011;95(2):327–39.

    Article  CAS  PubMed  Google Scholar 

  6. Rhodes C, White M. Molecular insights into insulin action and secretion. J Diabetes Investig. 2002;32(s3):3–13.

    CAS  Google Scholar 

  7. Egi M, Bellomo R, Stachowski E, French CJ, Hart G. Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology: Anesthesiology. 2006;105(2):244–52.

    Article  CAS  PubMed  Google Scholar 

  8. Donath MY, Ehses JA, Maedler K, Schumann DM, Ellingsgaard H, Eppler E, Reinecke M. Mechanisms of β-cell death in type 2 diabetes. Diabetes. 2005;54(suppl 2):S108–13.

    Article  CAS  PubMed  Google Scholar 

  9. Lupi R, Dotta F, Marselli L, Del Guerra S, Masini M, Santangelo C, et al. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets. Diabetes. 2002;51(5):1437–42.

    Article  CAS  PubMed  Google Scholar 

  10. Goyal Y, Verma AK, Joshi PC, Dev K. Contemplating the role of genetic variants of HHEX, CDKAL1, WFS1 and SLC30A8 genes of TYPE-2 diabetes in asians ethnic groups. Gene Rep. 2019;17:100465.

    Article  Google Scholar 

  11. Pal A, McCarthy MI. The genetics of type 2 diabetes and its clinical relevance. Clin Genet. 2013;83(4):297–306.

    Article  CAS  PubMed  Google Scholar 

  12. Li X, Li Y, Song B, Guo S, Chu S, Jia N, Niu W. Hematopoietically-expressed homeobox gene three widely-evaluated polymorphisms and risk for diabetes: a meta-analysis. PLoS ONE. 2012;7(11):e49917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bort R, Martinez-Barbera JP, Beddington RS, Zaret KS. Hex homeobox gene-dependent tissue positioning is required for organogenesis of the ventral pancreas. Development. 2004;131(4):797–806.

    Article  CAS  PubMed  Google Scholar 

  14. Hunter MP, Wilson CM, Jiang X, Cong R, Vasavada H, Kaestner KH, Bogue CW. The homeobox gene hhex is essential for proper hepatoblast differentiation and bile duct morphogenesis. Dev Biol. 2007;308(2):355–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pivovarova O, Nikiforova VJ, Pfeiffer AF, Rudovich N. The influence of genetic variations in HHEX gene on insulin metabolism in the German MESYBEPO cohort. Diabetes Metab Res Rev. 2009;25(2):156–62.

    Article  CAS  PubMed  Google Scholar 

  16. Marathe PH, Gao HX, Close KL. American Diabetes Association standards of medical care in diabetes 2017. J Diabetes. 2017;9(4):320–4.

    Article  PubMed  Google Scholar 

  17. Miller S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. van Vliet-Ostaptchouk JV, Onland-Moret NC, van Haeften TW, Franke L, Elbers CC, Shiri-Sverdlov R, et al. HHEX gene polymorphisms are associated with type 2 diabetes in the Dutch Breda cohort. Eur J Hum Genet. 2008;16(5):652–6.

    Article  PubMed  Google Scholar 

  19. Furukawa Y, Shimada T, Furuta H, Matsuno S, Kusuyama A, Doi A, et al. Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population. J Clin Endocrinol Metab. 2008;93(1):310–4.

    Article  CAS  PubMed  Google Scholar 

  20. Qian Y, Lu F, Dong M, Lin Y, Li H, Chen J, et al. Genetic variants of IDE-KIF11-HHEX at 10q23.33 associated with type 2 diabetes risk: a fine-mapping study in Chinese population. PLoS ONE. 2012;7(4):e35060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cai Y, Yi J, Ma Y, Fu D. Meta-analysis of the effect of HHEX gene polymorphism on the risk of type 2 diabetes. Mutagenesis. 2010;26(2):309–14.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to express their gratitude to T2DM patients for their participation in this study.

Funding

There was no funding to report.

Author information

Authors and Affiliations

Authors

Contributions

MH managed the project; SH drafted the manuscript and performed laboratory methods; MA performed the statistical analysis; MM, FAM, and HRAM: provided clinical guidance to the research. All authors contributed to and approved the final version of the manuscript.

Corresponding authors

Correspondence to Farhad Adhami Moghadam or Hamid Reza Aghaei Meybodi.

Ethics declarations

Consent for publication

All patients signed written consent forms and the study was approved by the ethical committee (Ethic Code: IR.TMU.REC.1395.19).

Competing interests

There are no conflicts of interest declared by the authors.

Additional information

Publisher’s Note

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

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hasti, S., Mirfeizi, M., Afshari, M. et al. Association of common single-nucleotide polymorphism of HHEX with type 2 diabetes mellitus. J Diabetes Metab Disord (2024). https://doi.org/10.1007/s40200-024-01407-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40200-024-01407-5

Keywords

Navigation