Skip to main content
SpringerLink
Log in

Association of +45(T/G) and +276(G/T) polymorphisms in the adiponectin gene with coronary artery disease in a population of Iranian patients with type 2 diabetes

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The relation of Two single nucleotide polymorphisms (SNPs) at the adiponectin locus (+45T/G and +276G/T) with coronary artery disease (CAD) is controversial. The aim of the present study was to evaluate the genetic influence of the adiponectin gene polymorphisms in the development of CAD among patients with Type 2 diabetes (T2D). The adiponectin genotypes were detected by polymerase chain reaction and restriction analysis (PCR-RFLP) in our patients. Two adiponectin gene (ADIPOQ) SNPs (i.e. SNPs +45T>G and +276G>T) were genotyped in 114 Type 2 diabetic subjects with CAD, and 127 Type 2 diabetic patients without CAD. Demographic and anthropometric data along with plasma biochemistry including lipids, glycemic indices, and adiponectin were collected. There was a significant difference in the distribution of genotypes of +45T/G and +276G/T between CAD and non-CAD individuals (P < 0.05). Based on our results SNP+276G>T is associated with decreased risk of CAD after adjustment for potential confounding factors [adjusted OR = 0.39 (95%CI: 0.22–0.68); P = 0.001]. Similar findings were not observed for the +45T>G SNP. Two haplotypes 45T-276T and 45G-276T were associated with a decreased risk of CAD [adjusted OR = 0.47 (95% CI: 0.32–0.94); P = 0.03 and adjusted OR = 0.33 (95% CI: 0.13–0.83); P = 0.02 respectively]. No significant difference was observed between HOMA-IR, BMI, waist circumference, history of hypertension, HbA1C, and lipid concentrations regarding the two SNPs. In conclusion, these findings suggest that T allele of +276G>T SNP is significantly associated with decreased risk of CAD in T2D Patients. Also Haplotype analysis showed that two haplotypes 45T-276T and 45G-276T were associated with a decreased risk of CAD.

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

References

  1. Stamler J, Vaccaro O, Neaton JD et al (1993) The Multiple Risk Factor Intervention Trial Research Group: Diabetes, other risk factors and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 16:434–444

    Article  PubMed  CAS  Google Scholar 

  2. Kannel WB, McGee DL (1979) Diabetes and cardiovascular disease: the Framingham Study. JAMA 241:2035–2038

    Article  PubMed  CAS  Google Scholar 

  3. Okamoto Y, Arita Y, Nishida M et al (2000) An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls (Abstract). Horm Metab Res 32:47A

    Article  Google Scholar 

  4. Goldstein BJ, Scalia RG, Ma XL (2009) Protective vascular and myocardial effects of adiponectin. Nat Clin Pract Cardiovasc Med. 6(1):27–35

    Article  PubMed  CAS  Google Scholar 

  5. Schnabel R, Messow CM, Lubos E et al (2008) Association of adiponectin with adverse outcome in coronary artery disease patients: results from the AtheroGene study. Eur Heart J 29(5):649–657

    Article  PubMed  CAS  Google Scholar 

  6. Sattar N, Wannamethee G, Sarwar N et al (2006) Adiponectin and coronary heart disease: a prospective study and meta-analysis. Circulation 114(7):623–629

    Article  PubMed  CAS  Google Scholar 

  7. Weyer C, Funahashi T, Tanaka S et al (2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935

    Article  PubMed  CAS  Google Scholar 

  8. Schwarz PE, Towers GW, Fischer S et al (2006) Hypoadiponectinemia is associated with progression toward type 2 diabetes and genetic variation in the ADIPOQ gene promoter. Diabetes Care 29:1645–1650

    Article  PubMed  CAS  Google Scholar 

  9. Thamer C, Haap M, Heller E et al (2006) Beta cell function, insulin resistance and plasma adiponectin concentrations are predictors for the change of postprandial glucose in non-diabetic subjects at risk for type 2 diabetes. Horm Metab Res 38:178–182

    Article  PubMed  CAS  Google Scholar 

  10. Qiao L, MacLean PS et al (2005) C/EBPa regulates human adiponectin gene transcription through an intronic enhancer. Diabetes 54:1744–1754

    Article  PubMed  CAS  Google Scholar 

  11. Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ et al (2000) The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab 280:E827–E847

    Google Scholar 

  12. Hu E, Liang P, Spiegelman BM (1996) AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 271:10697–10703

    Article  PubMed  CAS  Google Scholar 

  13. Maeda K, Okubo K, Shimomura I et al (1996) cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun 221:286–289

    Article  PubMed  CAS  Google Scholar 

  14. Nakano Y, Tobe T, Choi-Miura NH et al (1996) Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J Biochem 120:803–812

    PubMed  CAS  Google Scholar 

  15. Weyer C, Funahashi T, Tanaka S et al (2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinaemia. J Clin Endocrinol Metab 86:1930–1935

    Article  PubMed  CAS  Google Scholar 

  16. Acobellis G, Pistilli D, Gucciardo M et al (2005) Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease. Cytokine 29(6):251–255

    Google Scholar 

  17. Comuzzie AG, Funahashi T, Sonnenberg G et al (2001) The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab 86:4321–4325

    Article  PubMed  CAS  Google Scholar 

  18. Civitarese AE, Jenkinson CP, Richardson D et al (2004) Adiponectin receptors gene expression and insulin sensitivity in non-diabetic Mexican Americans with or without a family history of type 2 diabetes. Diabetologia 47:816–820

    Article  PubMed  CAS  Google Scholar 

  19. Stefan N, Vozarova B, Funahashi T et al (2002) Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes 51:1884–1888

    Article  PubMed  CAS  Google Scholar 

  20. Funahashi T, Nakamura T, Shimomura I, Maeda et al (1999) Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity. Intern Med 38:202–206

    Article  PubMed  CAS  Google Scholar 

  21. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE (2001) The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7:947–953

    Article  PubMed  CAS  Google Scholar 

  22. Ziccardi P, Nappo F, Giugliano G et al (2002) Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 105:804–809

    Article  PubMed  CAS  Google Scholar 

  23. Kubota N, Terauchi Y, Yamauchi T et al (2002) Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 277:25863–25866

    Article  PubMed  CAS  Google Scholar 

  24. Yamauchi T, Kamon J, Waki H et al (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946

    Article  PubMed  CAS  Google Scholar 

  25. Arita Y, Kihar S, Funahashi T et al (1998) Anovel adipocyte-derived factor, adiponectin, is decreased in obeity and coronary artery disease. Int J Obes 22:S40–S119

    Google Scholar 

  26. Kojima S, Funahashi T, Sakamoto T et al (2003) The variation of plasma concentrations of a novel, adipocyte derived protein, adiponectin, in patients with acute myocardial infarction. Heart 89(6):667

    Article  PubMed  CAS  Google Scholar 

  27. Kumada M, Kihara S, Sumitsuji S et al (2003) Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 23(1):85–89

    Article  PubMed  CAS  Google Scholar 

  28. Zoccali C, Mallamaci F, Tripepi G et al (2002) Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 13(1):134–141

    PubMed  CAS  Google Scholar 

  29. Pischon T, Girman CJ, Hotamisligil GS et al (2004) Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 291(14):1730–1737

    Article  PubMed  CAS  Google Scholar 

  30. Lindsay RS, Funahashi T, Hanson RL et al (2002) Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 360:57–58

    Article  PubMed  CAS  Google Scholar 

  31. Spranger J, Kroke A, Mohlig M et al (2003) Adiponectin and protection against type 2 diabetes mellitus. Lancet 361:226–228

    Article  PubMed  CAS  Google Scholar 

  32. Snehalatha C, Mukesh B, Simon M et al (2003) Plasma adiponectin is an independent predictor of type 2 diabetes in Asian Indians. Diabetes Care 26:3226–3229

    Article  PubMed  Google Scholar 

  33. Duncan BB, Schmidt MI, Pankow JS et al (2004) Adiponectin and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes 53:2473–2478

    Article  PubMed  CAS  Google Scholar 

  34. Frystyk J, Berne C, Berglund L et al (2007) Serum adiponectin is a predictor of coronary heart disease: a populationbased 10-year follow-up study in elderly men. J Clin Endocrinol Metab 92:571–576

    Article  PubMed  CAS  Google Scholar 

  35. Sattar N, Wannamethee G, Sarwar N et al (2006) Adiponectin and coronary heart disease: a prospective study and meta-analysis. Circulation 114:623–629

    Article  PubMed  CAS  Google Scholar 

  36. Takahashi M, Arita Y, Yamagata K et al (2000) Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes Relat Metab Disord 24:861–868

    Article  PubMed  CAS  Google Scholar 

  37. Vionnet N, Hani EH, Dupont S et al (2000) Genome-wide search for type 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21–24. Am J Hum Genet 67:1470–1480

    Article  PubMed  CAS  Google Scholar 

  38. Hara K, Boutin P, Mori Y et al (2002) Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 51:536–540

    Article  PubMed  CAS  Google Scholar 

  39. Vasseur F, Helbecque N, Dina C et al (2002) Single-nucleotide polymorphism haplotypes in both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet 11:2607–2614

    Article  PubMed  CAS  Google Scholar 

  40. Gu HF, Abulaiti A, Östenson C et al (2004) Single nucleotide polymorphisms in the proximal promoter region of the adiponectin (APM1) gene are associated with type 2 diabetes in Swedish Caucasians. Diabetes 53(Suppl 1):S31–S35

    Article  PubMed  CAS  Google Scholar 

  41. Stumvoll M, Tschritter O, Fritsche A et al (2002) Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity. Interaction with family history of type 2 diabetes. Diabetes 51:37–41

    Article  PubMed  CAS  Google Scholar 

  42. Lacquemant C, Froguel P, Lobbens S et al (2004) The adiponectin gene SNP+45 is associated with coronary artery disease in type 2 (non-insulin-dependent) diabetes mellitus. Diabet Med 21:776–781

    Article  PubMed  CAS  Google Scholar 

  43. Lee YY, Lee NS, Cho YM et al (2003) Genetic association of adiponectin polymorphisms with risk of type 2 diabetes mellitus. J Korean Diabetes Assoc 27:438–448

    Google Scholar 

  44. Nakamura Y, Shimada K, Fukuda D et al (2004) Implications of plasma concentrations of adiponectin in patients with coronary artery disease. Heart 90:528–533

    Article  PubMed  CAS  Google Scholar 

  45. Filippi E, Sentinelli F, Romeo S et al (2005) The adiponectin gene SNP+276G>T associates with early-onset coronary artery disease and with lower levels of adiponectin in younger coronary artery disease patients (age < or = 50 years). J Mol Med 83(9):711–719

    Article  PubMed  CAS  Google Scholar 

  46. Liu F, He Z, Deng S (2011) Association of adiponectin gene polymorphisms with the risk of ischemic stroke in a Chinese Han population. Mol Biol Rep 38(3):1983–1988

    Article  PubMed  CAS  Google Scholar 

  47. Qi L, Doria A, Manson JE et al (2006) Adiponectin genetic variability, plasma adiponectin, and cardiovascular risk in patients with type 2 diabetes. Diabetes 55(5):1512–1516

    Article  PubMed  CAS  Google Scholar 

  48. Kim SH, Kang ES, Hur KY et al (2008) Adiponectin gene polymorphism 45T>G is associated with carotid artery plaques in patients with type 2 diabetes mellitus. Metabolism 57:274–279

    Article  PubMed  CAS  Google Scholar 

  49. Zhang N, Shi Y-H, Hao C-F (2008) Association of C45G15G(T/G) and C276(G/T) polymorphisms in the ADIPOQ gene with polycystic ovary syndrome among Han Chinese women. Eur J Endocrinol 158:255–260

    Article  PubMed  CAS  Google Scholar 

  50. Takahashi M, Arita Y, Yamagata K et al (2000) Genomic structure and mutations in adiposespecific gene, adiponectin. Int J Obesity 24:861–868

    Article  CAS  Google Scholar 

  51. Filippi E, Sentinelli F, Trischitta V et al (2004) Association of the human adiponectin gene and insulin resistance. Eur J Hum Genet 12:199–205

    Article  PubMed  CAS  Google Scholar 

  52. Al-Daghri NM, Al-Attas OS et al (2011) Adiponectin gene variants and the risk of coronary artery disease in patients with type 2 diabetes. Mol Biol Rep. doi:10.1007/s11033-010-0484-5

  53. Bacci S, Menzaghi C, Ercolino T, Ma X, Rauseo A, Salvemini L et al (2004) The +276 G/T single nucleotide polymorphism of the adiponectin gene is associated with coronary artery disease in type 2 diabetic patients. Diabetes Care 27(8):2015–2020

    Article  PubMed  CAS  Google Scholar 

  54. Qi L, Li T, Rimm E, Zhang C et al (2004) The +276 polymorphism of the APM1 gene, plasma diponectin concentration, and cardiovascular risk in diabetic men. Diabetes 54(5):1607–1610

    Article  Google Scholar 

  55. Jang Y, Lee JH, Chae JS et al (2005) Association of the 276G → T polymorphism of the adiponectin gene with cardiovascular disease risk factors in nondiabetic Koreans. Am J Clin Nutr 82:760–767

    PubMed  CAS  Google Scholar 

  56. Pischon T, Pai JK, Manson JE et al (2007) Single nucleotide polymorphisms at the adiponectin locus and risk of coronary heart disease in men and women. Obesity (Silver Spring) 15(8):2051–2060

    Article  CAS  Google Scholar 

  57. Jung CH, Rhee EJ, Kim SY et al (2006) Associations between two single nucleotide polymorphisms of adiponectin gene and coronary artery diseases. Endocr J Oct 53(5):671–677

    Article  CAS  Google Scholar 

  58. Menzaghi C, Ercolino T, Di Paola R et al (2002) A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 51:2306–2312

    Article  PubMed  CAS  Google Scholar 

  59. Fumeron F, Aubert R, Siddiq A et al (2004) Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data Jung on the insulin resistance syndrome prospective study. Diabetes 53(4):1150–1157

    Article  PubMed  CAS  Google Scholar 

  60. Halvatsiotis I, Tsiotra PC, Ikonomidis I et al (2010) Genetic variation in the adiponectin receptor 2 (ADIPOR2) gene is associated with coronary artery disease and increased ADIPOR2 expression in peripheral monocytes. Cardiovasc Diabetol 9:10. doi:10.1186/1475-2840-9-10

    Article  PubMed  Google Scholar 

  61. Heid IM, Wagner SA, Gohlke H et al (2006) Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians. Diabetes 55(2):375–384

    Article  PubMed  CAS  Google Scholar 

  62. Ferrarezi DA, Cheurfa N, Reis AF et al (2006) Adiponectin gene and cardiovascular risk in Type 2 diabetic patients: a review of evidences. Arq Bras Endocrinol Metabol 51(2):153–159

    Article  Google Scholar 

Download references

Acknowledgments

The authors thank all the subjects for participating.

Conflict of interests

The authors declare no conflict of interests.

Author information

Authors and Affiliations

  1. Endocrine Research Center, Vali-asr Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Alireza Esteghamati, Nasrin Mansournia, Manouchehr Nakhjavani & Mehrshad Abbasi

  2. AJA University of Medical Sciences, Tehran, Iran

    Nasrin Mansournia

  3. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Ali Mansournia

  4. Department of Biochemistry, Faculty of Medicine, Ahvaz Jundi Shapour University of Medical Sciences, Ahvaz, Iran

    Abdolrahim Nikzamir

  5. Nutrition Research Center, Ahvaz Jundi Shapour University of Medical Sciences, Ahvaz, Iran

    Abdolrahim Nikzamir

  6. Research Institute for Nuclear Medicine and Molecular Imaging, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Mehrshad Abbasi

Authors
  1. Alireza Esteghamati
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nasrin Mansournia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manouchehr Nakhjavani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohammad Ali Mansournia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abdolrahim Nikzamir
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mehrshad Abbasi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abdolrahim Nikzamir.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Esteghamati, A., Mansournia, N., Nakhjavani, M. et al. Association of +45(T/G) and +276(G/T) polymorphisms in the adiponectin gene with coronary artery disease in a population of Iranian patients with type 2 diabetes. Mol Biol Rep 39, 3791–3797 (2012). https://doi.org/10.1007/s11033-011-1156-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-1156-9

Keywords

Search

Navigation