Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Genetic association of AKAP10 gene polymorphism with reduced risk of preterm birth

Journal of Perinatology volume 35, pages 700–704 (2015)Cite this article

Subjects

Abstract

Objective:

Preterm birth (PTB) is a multifactorial complication in which genetic and environmental factors contribute to the phenotype. The AKAP10 protein encoded by AKAP10 gene has a vital role in the maintenance of myometrial quiescence and pregnancy. This study aimed to investigate whether polymorphisms in the AKAP10 gene are associated with the risk of PTB.

Study design:

A total of 664 women (132 preterm and 532 term) with spontaneous singleton deliveries were genotyped for AKAP10 polymorphisms (rs119672, rs203462 and rs169412) using Sequenom MassARRAY platform.

Result:

A significant association was observed between the CC and AC genotypes of AKAP10 rs169412 with reduced risk of PTB (CC: adjusted odds ratio (OR) 2.95, 95% confidence interval (CI): 1.23–7.09, P=0.016. AC: adjusted OR 3.46, 95% CI: 1.38–8.68, P=0.008), respectively. Following stratification by ethnicity, a significant association was observed between the AC and CC genotypes of rs169412 and term birth in the Malay ethnic subgroup. (CC: OR 2.9, 95% CI: 1.01–8.59, P=0.041. AC: OR 3.14, 95% CI: 1.04–9.54, P=0.043). A significant association was also observed between the CT genotypes of AKAP10 rs119672 with reduced risk of PTB deliveries (CT: OR 3.2, 95% CI: 1.06–9.76 P=0.007, TT: OR 2.8, 0.98–8.34, P =.0.015) Alternatively, there was no association between AKAP10 rs169412 and rs119672 polymorphisms with PTB in the Indians and Chinese ethnic groups.

Conclusion:

This study indicates a significant association between the AKAP10 polymorphisms and reduced risk of PTB in the Malays. This demonstrates the potential role of AKAP10 polymorphisms in preterm complications.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Vogel J, Lee A, Souza J . Maternal morbidity and preterm birth in 22 low- and middle-income countries: a secondary analysis of the WHO Global Survey dataset. BMC Pregnancy Childbirth 2014; 14: 56.

    Article  Google Scholar 

  2. Ward RM, Beachy JC . Neonatal complications following preterm birth. BJOG 2001; 20: 8–16.

    Google Scholar 

  3. Zhang Y-P, Liu X-H, Gao S-H, Wang J-M, Gu Y-S, Zhang J-Y et al. Risk factors for preterm birth in five maternal and Child Health Hospitals in Beijing. PLoS One 2012; 7: e52780.

    Article  CAS  Google Scholar 

  4. Verli J, Klukovits A, Kormanyos Z, Hajagos-Toth J, Ducza E, Seres AB et al. Uterus-relaxing effect of beta2-agonists in combination with phosphodiesterase inhibitors: studies on pregnant rat in vivo and on pregnant human myometrium in vitro. J Obstet Gynaecol Res 2013; 39: 31–39.

    Article  Google Scholar 

  5. Price SA, Bernal AL . Uterine quiescence: the role of cyclic AMP. Exp Physiol 2001; 86: 265–272.

    Article  CAS  Google Scholar 

  6. MacDougall MW, Europe-Finner GN, Robson SC . Human myometrial quiescence and activation during gestation and parturition involve dramatic changes in expression and activity of particulate type II (RII alpha) protein kinase A holoenzyme. J Clin Endocrinol Metab 2003; 88: 2194–2205.

    Article  CAS  Google Scholar 

  7. Loniewska B, Clark JS, Kaczmarczyk M, Adler G, Binczak-Kuleta A, Kordek A et al. Possible counter effect in newborns of 1936 A>G (I646V) polymorphism in the AKAP10 gene encoding A-kinase-anchoring protein 10. J Perinatol 2012; 32: 230–234.

    Article  CAS  Google Scholar 

  8. Huang LJ, Durick K, Weiner JA, Chun J, Taylor SS . D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain. Proc Natl Acad Sci USA 1997; 94: 11184–11189.

    Article  CAS  Google Scholar 

  9. Ku CY, Sanborn BM . Progesterone prevents the pregnancy-related decline in protein kinase A association with rat myometrial plasma membrane and A-kinase anchoring protein. Biol Reprod 2002; 67: 605–609.

    Article  CAS  Google Scholar 

  10. Kim SH, Serezani CH, Okunishi K, Zaslona Z, Aronoff DM . Distinct protein kinase A anchoring proteins direct prostaglandin E2 modulation of Toll-like receptor signaling in alveolar macrophages. J Biol Chem 2011; 286: 8875–8883.

    Article  CAS  Google Scholar 

  11. Edwards AS, Scott JD . A-kinase anchoring proteins: protein kinase A and beyond. Curr Opin Cell Biol 2000; 12: 217–221.

    Article  CAS  Google Scholar 

  12. Amieux PS, McKnight GS . The essential role of RI alpha in the maintenance of regulated PKA activity. Ann NY Acad Sci 2002; 968: 75–95.

    Article  CAS  Google Scholar 

  13. Kammerer S, Burns-Hamuro LL, Ma Y, Hamon SC, Canaves JM, Shi MM et al. Amino acid variant in the kinase binding domain of dual-specific A kinase-anchoring protein 2: a disease susceptibility polymorphism. Proc Natl Acad Sci USA 2003; 100: 4066–4071.

    Article  CAS  Google Scholar 

  14. Tingley WG, Pawlikowska L, Zaroff JG, Kim T, Nguyen T, Young SG et al. Gene-trapped mouse embryonic stem cell-derived cardiac myocytes and human genetics implicate AKAP10 in heart rhythm regulation. Proc Natl Acad Sci USA 2007; 104: 8461–8466.

    Article  CAS  Google Scholar 

  15. Mehats C, Tanguy G, Paris B, Robert B, Pernin N . Pregnancy Induces a Modulation of the cAMP Phosphodiesterase 4-Conformers Ratio in Human Myometrium: Consequences for the Utero-Relaxant Effect of PDE4-Selective Inhibitors. J Pharmacol Exp Ther 2000; 292: 817–823.

    CAS  PubMed  Google Scholar 

  16. Teo YY, Sim X, Ong RT, Tan AK, Chen J, Tantoso E et al. Singapore Genome Variation Project: a haplotype map of three Southeast Asian populations. Genome Res 2009; 19: 2154–2162.

    Article  CAS  Google Scholar 

  17. Dolan SM . Genetic and environmental contributions to racial disparities in preterm birth. Mt Sinai J Med 2010; 77: 160–165.

    Article  Google Scholar 

  18. Engelhardt S, Zieger W, Kassubek J, Michel MC, Lohse MJ . Tocolytic therapy with fenoterol induces selective down-regulation of beta-adrenergic receptors in human myometrium. J Clin Endocrinol Metab 1997; 82: 1235–1242.

    CAS  PubMed  Google Scholar 

  19. Kosasa TS, Nakayama RT, Hale RW, Rinzler GS, Freitas CA . Ritodrine and terbutaline compared for the treatment of preterm labor. Acta Obstet Gynecol Scanda 1985; 64: 421–426.

    Article  CAS  Google Scholar 

  20. Phupong V, Charakorn C, Charoenvidhya D . Oral salbutamol for treatment of preterm labor. J Med Assoc Thai 2004; 87: 1012–1016.

    PubMed  Google Scholar 

  21. Klukovits A, Verli J, Falkay G, Gaspar R . Improving the relaxing effect of terbutaline with phosphodiesterase inhibitors: studies on pregnant rat uteri in vitro. Life Sci 2010; 87: 733–737.

    Article  CAS  Google Scholar 

  22. Soloff MS, Jeng YJ, Izban MG, Sinha M, Luxon BA, England SK . Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci 2011; 18: 781–797.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the patients and staffs of University of Malaya Medical Centre (UMMC) for their participation in this study. This study was funded by the University of Malaya research grant PG118-2012B and HIR MOHE E000025-20001.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Pharmacogenomics Laboratory, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

    I M Langmia, Y D Apalasamy, S Z Suki & Z Mohamed

  2. Department of Obstetrics and Gynecology, University of Malaya, Kuala Lumpur, Malaysia

    S Z Omar

Authors
  1. I M Langmia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y D Apalasamy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Z Suki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Z Omar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Z Mohamed
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Z Mohamed.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Langmia, I., Apalasamy, Y., Suki, S. et al. Genetic association of AKAP10 gene polymorphism with reduced risk of preterm birth. J Perinatol 35, 700–704 (2015). https://doi.org/10.1038/jp.2015.68

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2015.68

Search

Advanced search

Quick links