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:

Polymorphisms of the adiponectin gene in gestational hypertension and pre-eclampsia

Journal of Human Hypertension volume 28, pages 128–132 (2014)Cite this article

Subjects

Abstract

Adiponectin is a hormone involved in energy homeostasis by regulating glucose and lipid metabolism. In addition, the adiponectin gene (ADIPOQ) has polymorphisms that can modulate the circulating concentration of adiponectin. Abnormal adiponectin levels have been associated with pre-eclampsia (PE); however, the influence of genetic polymorphisms on the development of hypertensive disorders of pregnancy is unclear. The aim of this study was to examine whether ADIPOQ polymorphisms are associated with gestational hypertension (GH) and/or PE. We studied 401 pregnant women: 161 healthy pregnant (HP), 113 pregnant with GH and 127 pregnant with PE. ADIPOQ polymorphisms −11391G>A (rs17300539), −11377C>G (rs266729), 45T>G (rs2241766) and 276G>T (rs1501299) were genotyped by allelic discrimination assays using real-time PCR. Haplotypes were inferred using the PHASE 2.1 program. We observed that the genotypic frequencies of the −11377C>G polymorphism were different in PE compared with HP (P<0.0125), with the CT genotype being more commonly found in PE patients than in HP women (P<0.0125). However, allelic frequencies of this single-nucleotide polymorphism were similar between PE and HP (P>0.0125). No difference was observed when GH and HP groups were compared (both P>0.0125). In addition, we found no difference in genotype or allele distributions for the −11391G>A, 45T>G and 276G>T polymorphisms when we compared GH or PE with HP (all P>0.0125). In conclusion, we found a modest association between the CG genotype of the −11377C>G polymorphism and PE.

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

Similar content being viewed by others

References

  1. Redman CW, Sargent IL . Latest advances in understanding preeclampsia. Science 2005; 308 (5728): 1592–1594.

    Article  CAS  Google Scholar 

  2. Eiland E, Nzerue C, Faulkner M . Preeclampsia 2012. J Pregnancy 2012; 2012: 586578.

    Article  Google Scholar 

  3. Vitoratos N, Hassiakos D, Iavazzo C . Molecular mechanisms of preeclampsia. J Pregnancy 2012; 2012: 298343.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Pennington KA, Schlitt JM, Jackson DL, Schulz LC, Schust DJ . Preeclampsia: multiple approaches for a multifactorial disease. Dis Model Mech 2012; 5 (1): 9–18.

    Article  CAS  Google Scholar 

  5. McCarthy AL, Woolfson RG, Raju SK, Poston L . Abnormal endothelial cell function of resistance arteries from women with preeclampsia. Am J Obstet Gynecol 1993; 168 (4): 1323–1330.

    Article  CAS  Google Scholar 

  6. Zhou Y, Damsky CH, Fisher SJ . Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome? J Clin Invest 1997; 99 (9): 2152–2164.

    Article  CAS  Google Scholar 

  7. Zhu W, Cheng KK, Vanhoutte PM, Lam KS, Xu A . Vascular effects of adiponectin: molecular mechanisms and potential therapeutic intervention. Clin Sci 2008; 114 (5): 361–374.

    Article  CAS  Google Scholar 

  8. Benaitreau D, Dos Santos E, Leneveu MC, Alfaidy N, Feige JJ, de Mazancourt P et al. Effects of adiponectin on human trophoblast invasion. J Endocrinol 2010; 207 (1): 45–53.

    Article  CAS  Google Scholar 

  9. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K . Adiponectin and adiponectin receptors in obesity-linked insulin resistance. Novartis Found Symp. 2007; 286: 164–176 discussion 76-82, 200-3.

    Article  CAS  Google Scholar 

  10. Ohashi K, Ouchi N, Matsuzawa Y . Anti-inflammatory and anti-atherogenic properties of adiponectin. Biochimie 2012; 94 (10): 2137–2142.

    Article  CAS  Google Scholar 

  11. Ouchi N, Ohishi M, Kihara S, Funahashi T, Nakamura T, Nagaretani H et al. Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension 2003; 42 (3): 231–234.

    Article  CAS  Google Scholar 

  12. Aprahamian TR, Sam F . Adiponectin in cardiovascular inflammation and obesity. Int J Inflam 2011; 2011: 376909.

    Article  Google Scholar 

  13. Wang W, Xing W, Zhang H, Ding M, Shang L, Lau WB et al. Reduced high molecular weight adiponectin is an independent risk factor of cardiovascular lesions in hypercholesterolemic patients. Clin Endocrinol 2013; 78 (4): 539–544.

    Article  CAS  Google Scholar 

  14. Ramsay JE, Jamieson N, Greer IA, Sattar N . Paradoxical elevation in adiponectin concentrations in women with preeclampsia. Hypertension 2003; 42 (5): 891–894.

    Article  CAS  Google Scholar 

  15. Avci I, Ozerkan K, Uncu G . Serum adiponectin levels increase in lean preeclamptic women. Prenat Diagn 2010; 30 (1): 91–92.

    PubMed  Google Scholar 

  16. Menzaghi C, Ercolino T, Salvemini L, Coco A, Kim SH, Fini G et al. Multigenic control of serum adiponectin levels: evidence for a role of the APM1 gene and a locus on 14q13. Physiol Genomics 2004; 19 (2): 170–174.

    Article  CAS  Google Scholar 

  17. Park JW, Park J, Jee SH . ADIPOQ gene variants associated with susceptibility to obesity and low serum adiponectin levels in healthy Koreans. Epidemiol Health 2011; 33: e2011003.

    Article  Google Scholar 

  18. Chung HK, Chae JS, Hyun YJ, Paik JK, Kim JY, Jang Y et al. Influence of adiponectin gene polymorphisms on adiponectin level and insulin resistance index in response to dietary intervention in overweight-obese patients with impaired fasting glucose or newly diagnosed type 2 diabetes. Diabetes Care 2009; 32 (4): 552–558.

    Article  CAS  Google Scholar 

  19. Melistas L, Mantzoros CS, Kontogianni M, Antonopoulou S, Ordovas JM, Yiannakouris N . Association of the +45T&gt;G and +276G&gt;T polymorphisms in the adiponectin gene with insulin resistance in nondiabetic Greek women. Eur J Endocrinol 2009; 161 (6): 845–852.

    Article  CAS  Google Scholar 

  20. Leu HB, Chung CM, Lin SJ, Jong YS, Pan WH, Chen JW . Adiponectin gene polymorphism is selectively associated with the concomitant presence of metabolic syndrome and essential hypertension. PLoS ONE 2011; 6 (5): e19999.

    Article  CAS  Google Scholar 

  21. Jang Y, Chae JS, Koh SJ, Hyun YJ, Kim JY, Jeong YJ et al. The influence of the adiponectin gene on adiponectin concentrations and parameters of metabolic syndrome in non-diabetic Korean women. Clin Chim Acta 2008; 391 (1-2): 85–90.

    Article  CAS  Google Scholar 

  22. Avery PJ, Patel SK, Ibrahim IM, Walker M, Keavney BD . Common variation in the adiponectin gene has an effect on systolic blood pressure. J Hum Hypertens 2011; 25 (12): 719–724.

    Article  CAS  Google Scholar 

  23. Ong KL, Li M, Tso AW, Xu A, Cherny SS, Sham PC et al. Association of genetic variants in the adiponectin gene with adiponectin level and hypertension in Hong Kong Chinese. Eur J Endocrinol 2010; 163 (2): 251–257.

    Article  CAS  Google Scholar 

  24. Youpeng B, Wei X, Wei L, Jin J, Haiyan Y, Yuan Y et al. Relationships among adiponectin gene polymorphisms, proteinuria and increased blood pressure in the context of placental diseases. Hypertens Res 2010; 33 (10): 1066–1070.

    Article  Google Scholar 

  25. Saarela T, Hiltunen M, Helisalmi S, Heinonen S, Laakso M . Adiponectin gene haplotype is associated with preeclampsia. Genet Test 2006 Spring 10 (1): 35–39.

    Article  CAS  Google Scholar 

  26. Report of the National High Blood Pressure Education Program working group on high blood pressure in pregnancy. Am J Obstet Gynecol 2000; 183: S1–S22.

  27. Palei AC, Sandrim VC, Cavalli RC, Tanus-Santos JE . Comparative assessment of matrix metalloproteinase (MMP)-2 and MMP-9, and their inhibitors, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in preeclampsia and gestational hypertension. Clin Biochem 2008; 41 (10-11): 875–880.

    Article  CAS  Google Scholar 

  28. Sambrook DW JR . Molecular Cloning: a Laboratory Manual 3rd edn. USA, 2001.

    Google Scholar 

  29. Menzaghi C, Trischitta V, Doria A . Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease. Diabetes 2007; 56 (5): 1198–1209.

    Article  CAS  Google Scholar 

  30. Jang Y, Lee JH, Chae JS, Kim OY, Koh SJ, Kim JY et al. Association of the 276G-&gt;T polymorphism of the adiponectin gene with cardiovascular disease risk factors in nondiabetic Koreans. Am J Clin Nutr 2005; 82 (4): 760–767.

    Article  CAS  Google Scholar 

  31. Filippi E, Sentinelli F, Trischitta V, Romeo S, Arca M, Leonetti F et al. Association of the human adiponectin gene and insulin resistance. Eur J Hum Genet 2004; 12 (3): 199–205.

    Article  CAS  Google Scholar 

  32. Valenzuela FJ, Perez-Sepulveda A, Torres MJ, Correa P, Repetto GM, Illanes SE . Pathogenesis of preeclampsia: the genetic component. J Pregnancy 2012; 2012: 632732.

    Article  Google Scholar 

  33. Low CF, Mohd Tohit ER, Chong PP, Idris F . Adiponectin SNP45TG is associated with gestational diabetes mellitus. Arch Gynecol Obstet 2011; 283 (6): 1255–1260.

    Article  CAS  Google Scholar 

  34. Bouatia-Naji N, Meyre D, Lobbens S, Seron K, Fumeron F, Balkau B et al. ACDC/adiponectin polymorphisms are associated with severe childhood and adult obesity. Diabetes 2006; 55 (2): 545–550.

    Article  CAS  Google Scholar 

  35. Wang X, Zhang S, Chen Y, Liu H, Lan C, Chen X et al. APM1 gene variants -11377C/G and 4545G/C are associated respectively with obesity and with non-obesity in Chinese type 2 diabetes. Diabetes Res Clin Pract 2009; 84 (3): 205–210.

    Article  CAS  Google Scholar 

  36. Tanimura D, Shibata R, Izawa H, Hirashiki A, Asano H, Murase Y et al. Relation of a common variant of the adiponectin gene to serum adiponectin concentration and metabolic traits in an aged Japanese population. Eur J Hum Genet 2011; 19 (3): 262–269.

    Article  CAS  Google Scholar 

  37. Menzaghi C, Ercolino T, Di Paola R, Berg AH, Warram JH, Scherer PE et al. A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 2002; 51 (7): 2306–2312.

    Article  CAS  Google Scholar 

  38. Lee JY, Cho JK, Hong HR, Jin YY, Kang HS . Genetic effects of adiponectin single nucleotide polymorphisms on the clustering of metabolic risk factors in young Korean adults. Eur J Appl Physiol 2011; 112 (2): 623–629.

    Article  Google Scholar 

  39. Li LL, Kang XL, Ran XJ, Wang Y, Wang CH, Huang L et al. Associations between 45T/G polymorphism of the adiponectin gene and plasma adiponectin levels with type 2 diabetes. Clin Exp Pharmacol Physiol 2007; 34 (12): 1287–1290.

    Article  CAS  Google Scholar 

  40. Mousavinasab F, Tahtinen T, Jokelainen J, Koskela P, Vanhala M, Oikarinen J et al. Common polymorphisms (single-nucleotide polymorphisms SNP+45 and SNP+276) of the adiponectin gene regulate serum adiponectin concentrations and blood pressure in young Finnish men. Mol Genet Metab 2006; 87 (2): 147–151.

    Article  CAS  Google Scholar 

  41. Siitonen N, Pulkkinen L, Lindstrom J, Kolehmainen M, Eriksson JG, Venojarvi M et al. Association of ADIPOQ gene variants with body weight, type 2 diabetes and serum adiponectin concentrations: the Finnish Diabetes Prevention Study. BMC Med Genet 2011; 12: 5.

    Article  CAS  Google Scholar 

  42. Pena SD, Di Pietro G, Fuchshuber-Moraes M, Genro JP, Hutz MH, Kehdy Fde S et al. The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected. PLoS ONE 2011; 6 (2): e17063.

    Article  CAS  Google Scholar 

  43. Bader JS . The relative power of SNPs and haplotype as genetic markers for association tests. Pharmacogenomics 2001; 2 (1): 11–24.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by ‘Coordenação de Aperfeiçoamento de Pessoal de Nível Superior’ (CAPES). We thank Dr Joey P Granger, full professor in the Department of Physiology and Biophysics of the University of Mississippi Medical Center (Jackson/MS, USA), for his assistance in language editing of the manuscript.

Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil

    J S R Machado, G Duarte & R C Cavalli

  2. Department of Pharmacology, Faculty of Medicinal Sciences, State University of Campinas, Campinas, Brazil

    A C T Palei

  3. Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil

    L M Amaral & J E Tanus-Santos

  4. Department of Pediatrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil

    A C Bueno & S R Antonini

  5. Department of Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, Brazil

    V C Sandrim

Authors
  1. J S R Machado
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A C T Palei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L M Amaral
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A C Bueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S R Antonini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G Duarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J E Tanus-Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. V C Sandrim
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R C Cavalli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R C Cavalli.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Journal of Human Hypertension website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Machado, J., Palei, A., Amaral, L. et al. Polymorphisms of the adiponectin gene in gestational hypertension and pre-eclampsia. J Hum Hypertens 28, 128–132 (2014). https://doi.org/10.1038/jhh.2013.53

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2013.53

Keywords

This article is cited by

Search

Advanced search

Quick links