Skip to main content

Advertisement

SpringerLink
Log in

Angiotensin-converting enzyme insertion/deletion (I/D) polymorphisms and recurrent pregnancy loss: a meta-analysis

  • Review
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Background

Recurrent pregnancy loss (RPL) had said to be related to the angiotensin converting enzyme insertion/deletion polymorphisms (ACE I/D) gene polymorphisms. But the conclusions were controversial. This meta-analysis was conducted to investigate the real association in ACE I/D polymorphisms and RPL firstly.

Methods

Combine Pubmed Embase and HuGENet database in data analysis for this meta-analysis from October 2000 to November 2011. The metagen system was used to select the models and effects. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association.

Results

9 studies from six countries with 1264 RPL and 845 controls were included according to our criterion. Following the metagen system, we used the dominant model with random effects. The summary OR =1.61 (95% CI: 1.10-2.36, I 2 = 59.0%), which suggested the ACE D allele might increase the RPL risk in Asia (OR=1.97, 95% CI: 1.31-2.98, I 2 = 44.4%), among Asians (OR=1.69, 95% CI: 1.06-2.36, I 2 =32.7%). In additional, after conducting sensitivity analysis, the results had no differences except for Caucasian subgroup reached to the significance (OR=2.059, 95% CI: 1.455-2.914), so we couldn’t ignore the relationship between the polymorphisms of ACE D/I gene and Caucasians yet. There seemed no publication bias in our eligible studies with Begg’s test (P = 0.867).

Conclusions

Results in this meta-analysis presented the positive function of the ACE I/D polymorphism in increasing the RPL risk. Furfure prospective studies were needed to confirm the precise relationship between the ACE I/D and RPL.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Kempf Haber M, Klimek M. Thrombophilia in pregnancy and its influence on venous thromboembolism and recurrent miscarriages. Przegl Lek. 2005;62:164–8.

    PubMed  Google Scholar 

  2. Sayed-Tabatabaei FA, Oostra BA, Isaacs A, van Duijn CM, Witteman JC. ACE polymorphisms. Circ Res. 2006;98:1123–33.

    Article  PubMed  CAS  Google Scholar 

  3. Ueda S, Elliott HL, Morton JJ, Connell JM. Enhanced pressor response to angiotensin I in normotensive men with the ACE deletion allele. Hypertension. 1995;25:1266–9.

    Article  PubMed  CAS  Google Scholar 

  4. Buchholz T, Thaler CJ. Inherited thrombophilia: impact on human reproduction. Am J Reprod Immunol. 2003;49:1–13.

    Article  Google Scholar 

  5. Wiwanitkit V. Angiotensin-converting enzyme gene polymorphism: I and D alleles from some different countries. Clin Appl Thromb Hemost. 2004;10:179–82.

    Article  PubMed  CAS  Google Scholar 

  6. Rigat B, Hubert C, Alhenc-Gelas F, Caambien F, Corvol P, Soubrier F. An insertion ⁄ deletion polymorphism in the angiotensin I converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990;86:1343–6.

    Article  PubMed  CAS  Google Scholar 

  7. Fatini C, Gensini F, Sticchi E, Battaglini B, Prisco D, Fedi S, et al. ACE DD genotype: an independent predisposition factor to venous thromboembolism. Eur J Clin Invest. 2003;33:642–7.

    Article  PubMed  CAS  Google Scholar 

  8. Kim DK, Kim JW, Kim S, Gwon HC, Ryu JC, Huh JE, et al. Polymorphism of angiotensin converting enzyme gene is associated with circulating levels of plasminogen activator inhibitor-1. Arterioscler Thromb Vasc Biol. 1997;17:3242–7.

    Article  PubMed  CAS  Google Scholar 

  9. Sarig G, Younis JS, Hoffman R, Lanir N, Blumenfeld Z, Brenner B. Thrombophilia is common in women with idiopathic pregnancy loss and is associated with late pregnancy wastage. Fertil Steril. 2002;77:342–7.

    Article  PubMed  Google Scholar 

  10. Younis JS, Ohel G, Brenner B, Ben-Ami M. Familial thrombophilia—the scientific rationale for thrombophylaxis in recurrent pregnancy loss? Hum Reprod. 1997;12:1389–90.

    Article  PubMed  CAS  Google Scholar 

  11. Fatini C, Gensini F, Battaglini B, Prisco D, Cellai AP, Fedi S, et al. Angiotensin-converting enzyme DD genotype, angiotensin type 1 receptor CC genotype, and hyperhomocysteinemia increase firsttrimester fetal-loss susceptibility. Blood Coagul Fibrinolysis. 2000;11:657–62.

    Article  PubMed  CAS  Google Scholar 

  12. Dossenbach-Glaninger A, van Trotsenburg M, Schneider B, Oberkanins C, Hopmeier P. ACE I/D polymorphism and recurrent first trimester pregnancy loss: interaction with SERPINE1 4G/5G and F13 Val34Leu polymorphisms. Br J Haematol. 2008;141:269–71.

    Article  PubMed  Google Scholar 

  13. Middeldorp S. Pregnancy failure and heritable thrombophilia. Semin Hematol. 2007;44:93–7.

    Article  PubMed  Google Scholar 

  14. Eldor A. Thrombophilia, thrombosis and pregnancy. Thromb Haemost. 2001;86:104–11.

    PubMed  CAS  Google Scholar 

  15. Carp H, Salomon O, Seidman D, Dardik R, Rosenberg N, Inbal A. Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Hum Reprod. 2002;17:1633–7.

    Article  PubMed  Google Scholar 

  16. Prandoni P, Tormene D, Simioni P, Girolami A. Venous thromboembolism, fetal loss and preeclampsia in pregnant women with congenital thrombophilia. Clin Lab. 2001;47:155–9.

    PubMed  CAS  Google Scholar 

  17. Di Micco P, D’Uva M, Strina I, De Placido G, Di Fiore R, Quaranta S, et al. Recurrent pregnancy loss and thrombophilia. Clin Lab. 2007;53:309–14.

    PubMed  Google Scholar 

  18. Su MT, Lin SH, Chen YC. Association of sex hormone receptor gene polymorphisms with recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril. 2011;96:1435–44.

    Article  PubMed  CAS  Google Scholar 

  19. Su MT, Lin SH, Chen YC. Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod Update. 2011;17:803–12.

    Article  PubMed  CAS  Google Scholar 

  20. Ostojic S, Pereza N, Kastrin A, Peterlin B. Association between genetic polymorphisms in cytokine genes and recurrent miscarriage–a meta-analysis. Reprod Biomed Online. 2009;19:406–14.

    Article  PubMed  Google Scholar 

  21. Nelen WL, Blom HJ, Steegers EA, den Heijer M, Eskes TK. Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril. 2000;74:1196–9.

    Article  PubMed  CAS  Google Scholar 

  22. Egger M, Davey Smith G, Schneider M, Minder C. Bias in metaanalysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  PubMed  CAS  Google Scholar 

  23. Li H, Ha TC, Tai BC. XRCC1 gene polymorphisms and breast cancer risk in different populations: A meta-analysis. Breast. 2009;18:183–91.

    Article  PubMed  CAS  Google Scholar 

  24. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127:820–6.

    PubMed  CAS  Google Scholar 

  25. Vettriselvi V, Vijayalakshmi K, Paul SF, Venkatachalam P. ACE and MTHFR gene polymorphisms in unexplained recurrent pregnancy loss. J Obstet Gynaecol Res. 2008;34:301–6.

    Article  PubMed  CAS  Google Scholar 

  26. Choi YS, Kwon H, Kim JH, Shin JE, Choi Y, Yoon TK, et al. Haplotype-based association of ACE I/D, AT1R 1166A>C, and AGT M235T polymorphisms in renin–angiotensin–aldosterone system genes in Korean women with idiopathic recurrent spontaneous abortions. Eur J Obstet Gynecol Reprod Biol. 2011;158:225–8.

    Article  PubMed  CAS  Google Scholar 

  27. Bukreeva L, Grigorov A, Kiesewetter H, Hoppe B. Association of angiotensin-converting enzyme intron 16 insertion/deletion polymorphism with history of foetal loss. J Renin Angiotensin Aldosterone Syst. 2009;10:237–40.

    Article  PubMed  CAS  Google Scholar 

  28. Mello G, Parretti E, Gensini F, Sticchi E, Mecacci F, Scarselli G, et al. Maternal-Fetal Flow, Negative Events, and Preeclampsia Role of ACE I/D Polymorphism. Hypertension. 2003;41:932–7.

    Article  PubMed  CAS  Google Scholar 

  29. Yenicesu GI, Cetin M, Ozdemir O, Cetin A, Ozen F, Yenicesu C, et al. A Prospective Case–Control Study Analyzes 12 Thrombophilic Gene Mutations in Turkish Couples with Recurrent Pregnancy Loss. Am J Reprod Immunol. 2010;63:126–36.

    Article  PubMed  Google Scholar 

  30. Buchholz T, Lohse P, Rogenhofer N, Kosian E, Pihusch R, Thaler CJ. Polymorphisms in the ACE and PAI-1 genes are associated with recurrent spontaneous miscarriages. Hum Reprod. 2003;18:2473–7.

    Article  PubMed  CAS  Google Scholar 

  31. Goodman C, Hur J, Goodman CS, Jeyendran RS, Coulam C. Are Polymorphisms in the ACE and PAI-1 Genes Associated with Recurrent Spontaneous Miscarriages? Am J Reprod Immunol. 2009;62:365–70.

    Article  PubMed  CAS  Google Scholar 

  32. Al Sallout RJ, Sharif FA. Polymorphisms in NOS3, ACE and PAI-1 Genes and Risk of Spontaneous Recurrent Miscarriage in the Gaza Strip. Med Princ Pract. 2010;19:99–104.

    Article  PubMed  Google Scholar 

  33. Bagheri M. Abdi Rad I, Omrani MD, Nanbaksh F. Polymorphisms of the angiotensin converting enzyme gene in Iranian Azeri Turkish women with unexplained recurrent pregnancy loss. Hum Fertil (Camb). 2010;13:79–82.

    Article  CAS  Google Scholar 

  34. Corbo RM, Ulizzi L, Piombo L, Scacchi R. Association of ACE I/D polymorphism and recurrent miscarriages in an Italian population with a pre-modern reproductive pattern. Ann Hum Biol. 2011;38:102–5.

    Article  PubMed  CAS  Google Scholar 

  35. Aarabi M, Memariani T, Arefi S, Aarabi M. Hantoosh Zadeh S, Akhondi MA, Modarressi MH. Polymorphisms of plasminogen activator inhibitor-1, angiotensin converting enzyme and coagulation factor XIII genes in patients with recurrent spontaneous abortion. J Matern Fetal Neonatal Med. 2011;24:545–8.

    Article  PubMed  CAS  Google Scholar 

  36. Zhang S, Wang J, Wang B, Ping Y, Ma X. Strong Association Between Angiotensin I-Converting Enzyme I/D Polymorphism and Unexplained Recurrent Miscarriage of Chinese Women—A Case–Control Study. Reprod Sci. 2011;18:743–6.

    Article  PubMed  Google Scholar 

  37. Ozdemir O, Yenicesu GI, Silan F, Köksal B, Atik S, Ozen F et al. Recurrent Pregnancy Loss and Its Relation to Combined Parental Thrombophilic Gene Mutations. Genet Test Mol Biomarkers. 2011; 2: [Epub ahead of print].

Download references

Acknowledgments

This study was partially supported by grants from the Guangxi major disease prevention and control of new technology research and development (1298003-6-4), Guangxi Population Research Foundation (1104) from Guangxi family planning commission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China

    Chen Yang, Li Jie, Yang Yanlong, Wang Jie & Hu Yanling

  2. Medical Research Center, Guangxi Medical University, NO.22 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, 530021, China

    Wu Fangfang, Zhang Xuerong & Hu Yanling

  3. Guangxi Plan Reproductive Research Institute, Nanning, Guangxi, China

    Liang Xuefei

Authors
  1. Chen Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wu Fangfang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li Jie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yang Yanlong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wang Jie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Liang Xuefei
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhang Xuerong
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hu Yanling
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zhang Xuerong or Hu Yanling.

Additional information

Capsule ACE D/I polymorphism increase the RPL risk.

Chen Yang, Wu Fangfang and Li Jie-These authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, C., Fangfang, W., Jie, L. et al. Angiotensin-converting enzyme insertion/deletion (I/D) polymorphisms and recurrent pregnancy loss: a meta-analysis. J Assist Reprod Genet 29, 1167–1173 (2012). https://doi.org/10.1007/s10815-012-9870-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-012-9870-3

Keywords

Search

Navigation