Skip to main content

Advertisement

SpringerLink
Log in

Association of eNOS and ACE gene polymorphisms as a genetic risk factor in gestational diabetes in Iranian women

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

A Correction to this article was published on 25 June 2020

This article has been updated

Abstract

Background

Gestational diabetes mellitus (GDM) is the most popular metabolic disease during pregnancy. The aim of the present study was to investigate any possible association between eNOS Glu298Asp and ACE I/D gene polymorphisms and the risk of GDM in a group of Iranian pregnant women.

Methods

In this case-control study 204 pregnant women were recruited (94 cases and 110 controls). Genomic DNA was isolated from whole blood and genotyping was performed by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR- RFLP) and only PCR for eNOS and ACE polymorphisms respectively.

Results

Frequencies of GT and TT genotype of eNOS polymorphism among women with and without GDM were 67.90% vs. 74.47 and 7.41% vs. 8.51% respectively (P = 0.4). Corresponding figures for DD genotype of ACE polymorphism among GDM patients was more than that in healthy women (51.65% vs. 63.81% respectively). Conversely, ACE heterozygote genotype was more common in diabetic women (35.16% vs. 26.67% respectively). Although these differences were not statistically significant (P = 0.2).

Conclusions

Our study showed that there is no association between the presence of eNOS and ACE gene polymorphisms and developing gestational diabetes mellitus among pregnant women in our population. Further longitudinal and multicenter studies should be carried out to assess the exact metabolic effects of these polymorphisms.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Change history

  • 25 June 2020

    The authors would like to clarify that Shahnaz Babayanzad Ahari was incorrectly removed from the original article and should be included in the authorship.

Abbreviations

T2D:

Type 2 Diabetes

GDM:

Gestational Diabetes Mellitus

eNOS :

endothelial Nitric Oxide Synthase

ACE :

Angiotensin Converting Enzyme

OGCT:

Oral Glucose Challenge Test

T1DM:

Type 1 Diabetes Mellitus

BMI:

Body Mass Index

ADA:

American Diabetes Association

I/D:

Insertion/Deletion.

References

  1. Coustan DR. Gestational diabetes mellitus. Clin Chem. 2013;59(9):1310–21.

    Article  CAS  Google Scholar 

  2. Zhang Y, Sun C-M, Hu X-Q, Zhao Y. Relationship between melatonin receptor 1B and insulin receptor substrate 1 polymorphisms with gestational diabetes mellitus: a systematic review and meta-analysis. Sci Rep 2014;4:6113.

  3. Kamana K, Shakya S, Zhang H. Gestational diabetes mellitus and macrosomia: a literature review. Ann Nutr Metab. 2015;66(Suppl. 2):14–20.

    Google Scholar 

  4. Morris AP, Voight BF, Teslovich TM, Ferreira T, Segre AV, Steinthorsdottir V, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet. 2012;44(9):981–90.

    Article  CAS  Google Scholar 

  5. Santos KG, Crispim D, Canani LH, Ferrugem PT, Gross JL, Roisenberg I. Association of eNOS gene polymorphisms with renal disease in Caucasians with type 2 diabetes. Diabetes Res Clin Pract. 2011;91(3):353–62.

    Article  CAS  Google Scholar 

  6. Dudzinski DM, Michel T. Life history of eNOS: partners and pathways. Cardiovasc Res. 2007;75(2):247–60.

    Article  CAS  Google Scholar 

  7. Förstermann U. Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies. Nat Clin Pract Cardiovasc Med. 2008;5(6):338–49.

    Article  Google Scholar 

  8. Wattanapitayakul SK, Mihm MJ, Young AP, Bauer JA. Therapeutic implications of human endothelial nitric oxide synthase gene polymorphism. Trends Pharmacol Sci. 2001;22(7):361–8.

    Article  CAS  Google Scholar 

  9. Ziaei S, Samzadeh M, Jamaldini SH, Afshari M, Haghdoost AA, Hasanzad M. Endothelial nitric oxide synthase Glu298Asp polymorphism as a risk factor for prostate cancer. Int J Biol Markers. 2013;28(1):43–8.

    Article  CAS  Google Scholar 

  10. Marsden PA, Heng H, Scherer S, Stewart R, Hall A, Shi X, et al. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem. 1993;268(23):17478–88.

    CAS  PubMed  Google Scholar 

  11. Ezzidi I, Mtiraoui N, Mohamed MBH, Mahjoub T, Kacem M, Almawi WY. Association of endothelial nitric oxide synthase Glu298Asp, 4b/a, and− 786T> C gene variants with diabetic nephropathy. J Diabetes Complicat. 2008;22(5):331–8.

    Article  Google Scholar 

  12. Sayed-Tabatabaei F, Oostra B, Isaacs A, Van Duijn C, Witteman J. ACE polymorphisms. Circ Res. 2006;98(9):1123–33.

    Article  CAS  Google Scholar 

  13. Rigat B, Hubert C, Corvol P, Soubrier F. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1)(dipeptidyl carboxypeptidase 1). Nucleic Acids Res. 1992;20(6):1433.

    Article  CAS  Google Scholar 

  14. Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F, et al. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet. 1992;51(1):197–205.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Baudin B. Angiotensin II receptor polymorphisms in hypertension. Pharmacogenomic Considerations Pharmacogenomics. 2002;3(1):65–73.

    CAS  PubMed  Google Scholar 

  16. Henriksen EJ, Jacob S. Effects of captopril on glucose transport activity in skeletal muscle of obese Zucker rats. Metabolism. 1995;44(2):267–72.

    Article  CAS  Google Scholar 

  17. İlhan N, Ateş K, İlhan N, Kaman D, Çeliker H. eNOS Glu298Asp polymorphism and endothelial dysfunction in patients with and without end-stage renal disease. Balkan Med J. 2016;33(2):128–37.

    Article  Google Scholar 

  18. Martinelli NC, Santos KG, Biolo A, La Porta VL, Cohen CR, Silvello D, et al. Polymorphisms of endothelial nitric oxide synthase gene in systolic heart failure: an haplotype analysis. Nitric Oxide. 2012;26(3):141–7.

    Article  CAS  Google Scholar 

  19. Thameem F, Puppala S, Arar NH, Stern MP, Blangero J, Duggirala R, et al. Endothelial nitric oxide synthase (eNOS) gene polymorphisms and their association with type 2 diabetes-related traits in Mexican Americans. Diab Vasc Dis Res. 2008;5(2):109–13.

    Article  Google Scholar 

  20. Haijuan H, Fan Z, Meilin Z, Guifen C, Haiyun H, Pinff H. Relationship between endothelial nitric oxide synthase Glu298Asp gene polymorphisms and the chronic periodontitis with type 2 diabetes mellitus. Hua Xi Kou Qiang Yi Xue Za Zhi. 2012;30(6):628–31.

  21. Atay AE, Akbas H, Tumer C, Sakar MN, Esen B, Incebiyik A, et al. The association of endothelial nitric oxide synthase gene G894T polymorphism and serum nitric oxide concentration with microalbuminuria in patients with gestational diabetes. Clin Nephrol. 2014;81(2):105–11.

    Article  CAS  Google Scholar 

  22. Daimon M, Oizumi T, Saitoh T, Kameda W, Hirata A, Yamaghchi H, et al. The D allele of the angiotensin-converting enzyme insertion/deletion (I/D) polymorphism is a risk factor for type 2 diabetes in a population-based Japanese sample. Endocr J. 2003;50(4):393–8.

    Article  CAS  Google Scholar 

  23. Degirmenci I, Kebapci N, Basaran A, Efe B, Gunes H, Akalin A, et al. Frequency of angiotensin-converting enzyme gene polymorphism in Turkish type 2 diabetic patients. Int J Clin Pract. 2005;59(10):1137–42.

    Article  CAS  Google Scholar 

  24. Hsieh MC, Lin SR, Hsieh TJ, Hsu CH, Chen HC, Shin SJ, et al. Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan. Nephrol Dial Transplant. 2000;15(7):1008–13.

    Article  CAS  Google Scholar 

  25. Liyun L, Songbiao L, Chengshan W, Xiufang L. Left ventricular diastolic dysfunction and obesity: a systematic review and meta-analysis of echocardiographic studies. International Journal of Cardiovascular and Cerebrovascular Disease. 2016;4(3):27–34.

  26. Dostálová Z, Bienertová-Vasků A, Vasků A, Gerychová R, Unzeitig V. Insertion-deletion polymorphism in the gene for angiotensin-converning enzyme (I/D ACE) in pregnant women with gestational diabetes. Ceska Gynekol. 2006;71(5):369–73.

    PubMed  Google Scholar 

  27. Khan IA, Jahan P, Hasan Q, Rao P. Angiotensin-converting enzyme gene insertion/deletion polymorphism studies in Asian Indian pregnant women biochemically identifies gestational diabetes mellitus. J Renin-Angiotensin-Aldosterone Syst. 2014;15(4):566–71.

    Article  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the contribution of the subjects in this study. The authors would like to thank all gestational diabetic patients who involved in this survey. And this study was supported by Karaj Branch, Islamic Azad University, Alborz, Iran.

Funding

This study was supporting by Karaj Branch, Islamic Azad University, Alborz, Iran.

Author information

Authors and Affiliations

  1. Department of Midwifery, College of Nursing & Midwifery, Islamic Azad University, Karaj Branch, Moazen Blvd and Esteglal Blvd Rajaeishahr, Karaj, Alborz, 1916893813, Iran

    Mani Mirfeizi & Zarin Ajoodani

  2. Medical Genomics Research Center, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran

    Mandana Hasanzad & Mahshid Sattari

  3. Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Mandana Hasanzad

  4. Department of Community Medicine, Zabol University of Medical Sciences, Zabol, Iran

    Mahdi Afshari

  5. Iranian Diabetes Society, Eslamshahr Branch, Eslamshahr, Iran

    Davood Abbasi

  6. Alborz Hospital, Alborz, Iran

    Zarin Ajoodani

  7. Ghaem Hospital, Alborz, Iran

    Ali Bani Sheykheslam

Authors
  1. Mani Mirfeizi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mandana Hasanzad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mahshid Sattari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mahdi Afshari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Davood Abbasi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zarin Ajoodani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ali Bani Sheykheslam
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MM: conceived and designed the present study and gave final approval and critically revised the manuscript; MH: designed the Genetic study; MS: technical Genetic laboratory; MA: Statistical analysis; DA: sample collection & clinical study; ZA: sample collection; ZB: sample collection; AB: sample collection.

Corresponding author

Correspondence to Mani Mirfeizi.

Ethics declarations

Competing interests

The authors declare that there is no conflict of interest.

Consent for publication

Oral and written consent were obtained from the patients.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mirfeizi, M., Hasanzad, M., Sattari, M. et al. Association of eNOS and ACE gene polymorphisms as a genetic risk factor in gestational diabetes in Iranian women. J Diabetes Metab Disord 17, 123–127 (2018). https://doi.org/10.1007/s40200-018-0348-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-018-0348-4

Keywords

Search

Navigation