Skip to main content
SpringerLink
Log in

Associations between C1431T and Pro12Ala variants of PPARγ gene and their haplotypes with susceptibility to metabolic syndrome in an Iranian population

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor that regulates a number of genes involved in lipid and carbohydrate metabolism. The aim of this study was to investigate the association of C1431T and Pro12Ala polymorphisms of PPARγ gene and their haplotypes and diplotypes with risk of metabolic syndrome (MetS) in an Iranian population. A total of 340 unrelated Iranian subjects, including 175 MetS patients and 165 normal controls were enrolled. Each group was then divided into two subgroups according to the genotype (Pro/Pro and Pro/Ala + Ala/Ala for Pro12Ala, CC and CT + TT for C1431T). Genotypes were determined using a TaqMan method. Anthropometric indices, fasting plasma glucose and fasting lipid profile were measured by routine methods. A significant difference in the frequencies of the C1431T genotypes was observed between MetS and control subjects (P = 0.014), whereas no association was found for the Pro12Ala. The T allele carriers had a significantly increased risk of MetS compared to the CC genotype (P = 0.016) even after correction for multiple-testing and adjustment for age, sex and genotype. The T allele may therefore be considered as a risk factor for MetS (P = 0.003). Analysis of combined groups showed that X/Ala-CC and Pro/Pro-X/T diplotypes were associated with a higher body weight, waist circumference and waist to hip ratio among the individuals with MetS. Moreover the Ala-T haplotype was weakly associated with a higher level of triglyceride and lower level of HDL, suggesting the possibility of an interaction between Ala and T alleles. This study suggests that the PPARγ C1431T polymorphism is related to an increased risk of MetS in an Iranian population and interacts with the Pro12Ala polymorphism, further increasing the risk of MetS.

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. Denke MA, Pasternak RC (2001) Defining and treating the metabolic syndrome: a primer from the adult treatment panel III. Curr Treat Options Cardiovasc Med 3:251–253

    Article  PubMed  Google Scholar 

  2. Eckel RH, Grundy SM, Zimmet PZ (2005) The metabolic syndrome. Lancet 365:1415–1428

    Article  CAS  PubMed  Google Scholar 

  3. Bruce KD, Hanson MA (2010) The developmental origins, mechanisms, and implications of metabolic syndrome. J Nutr 140:648–652

    Article  CAS  PubMed  Google Scholar 

  4. Gotoda T (2004) Genetic susceptibility to metabolic syndrome. Nihon Rinsho 62:1037–1044

    PubMed  Google Scholar 

  5. Monda KL, North KE, Hunt SC, Rao DC, Province MA et al (2010) The genetics of obesity and the metabolic syndrome. Endocr Metab Immune Disord Drug Targets 10:86–108

    Article  CAS  PubMed  Google Scholar 

  6. Kristiansson K, Perola M, Tikkanen E, Kettunen J, Surakka I et al (2012) Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits. Circ Cardiovasc Genet 5:242–249

    Article  PubMed Central  PubMed  Google Scholar 

  7. Desvergne B, Wahli W (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 20:649–688

    CAS  PubMed  Google Scholar 

  8. Fajas L, Debril MB, Auwerx J (2001) Peroxisome proliferator-activated receptor-gamma: from adipogenesis to carcinogenesis. J Mol Endocrinol 27:1–9

    Article  CAS  PubMed  Google Scholar 

  9. Meirhaeghe A, Amouyel P (2004) Impact of genetic variation of PPARgamma in humans. Mol Genet Metab 83:93–102

    Article  CAS  PubMed  Google Scholar 

  10. Yen CJ, Beamer BA, Negri C, Silver K, Brown KA et al (1997) Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun 241:270–274

    Article  CAS  PubMed  Google Scholar 

  11. Altshuler D, Hirschhorn JN, Klannemark M, Lindgren CM, Vohl MC et al (2000) The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 26:76–80

    Article  CAS  PubMed  Google Scholar 

  12. Huguenin GV, Rosa G (2010) The Ala allele in the PPAR-gamma2 gene is associated with reduced risk of type 2 diabetes mellitus in Caucasians and improved insulin sensitivity in overweight subjects. Br J Nutr 104:488–497

    Article  CAS  PubMed  Google Scholar 

  13. Doney AS, Fischer B, Cecil JE, Boylan K, McGuigan FE et al (2004) Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes. Diabetologia 47:555–558

    Article  CAS  PubMed  Google Scholar 

  14. Meshkani R, Taghikhani M, Larijani B, Bahrami Y, Khatami S et al (2007) Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma-2) gene is associated with greater insulin sensitivity and decreased risk of type 2 diabetes in an Iranian population. Clin Chem Lab Med 45:477–482

    Article  CAS  PubMed  Google Scholar 

  15. Masud S, Ye S (2003) Effect of the peroxisome proliferator activated receptor-gamma gene Pro12Ala variant on body mass index: a meta-analysis. J Med Genet 40:773–780

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Deeb SS, Fajas L, Nemoto M, Pihlajamaki J, Mykkanen L et al (1998) A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 20:284–287

    Article  CAS  PubMed  Google Scholar 

  17. Ostgren CJ, Lindblad U, Melander O, Melander A, Groop L et al (2003) Peroxisome proliferator-activated receptor-gammaPro12Ala polymorphism and the association with blood pressure in type 2 diabetes: skaraborg hypertension and diabetes project. J Hypertens 21:1657–1662

    Article  PubMed  Google Scholar 

  18. Tai ES, Corella D, Deurenberg-Yap M, Adiconis X, Chew SK et al (2004) Differential effects of the C1431T and Pro12Ala PPARgamma gene variants on plasma lipids and diabetes risk in an Asian population. J Lipid Res 45:674–685

    Article  CAS  PubMed  Google Scholar 

  19. Zhou X, Chen J, Xu W (2012) Association between C1431T polymorphism in peroxisome proliferator-activated receptor-gamma gene and coronary artery disease in Chinese Han population. Mol Biol Rep 39:1863–1868

    Article  CAS  PubMed  Google Scholar 

  20. Wang XL, Oosterhof J, Duarte N (1999) Peroxisome proliferator-activated receptor gamma C161–>T polymorphism and coronary artery disease. Cardiovasc Res 44:588–594

    Article  CAS  PubMed  Google Scholar 

  21. Rhee EJ, Oh KW, Lee WY, Kim SY, Oh ES et al (2006) Effects of two common polymorphisms of peroxisome proliferator-activated receptor-gamma gene on metabolic syndrome. Arch Med Res 37:86–94

    Article  CAS  PubMed  Google Scholar 

  22. Shi H, Yu X, Li Q, Ye X, Gao Y et al (2012) Association between PPAR-gamma and RXR-alpha gene polymorphism and metabolic syndrome risk: a case-control study of a Chinese Han population. Arch Med Res 43:233–242

    Article  CAS  PubMed  Google Scholar 

  23. Dongxia L, Qi H, Lisong L, Jincheng G (2008) Association of peroxisome proliferator-activated receptorgamma gene Pro12Ala and C161T polymorphisms with metabolic syndrome. Circ J 72:551–557

    Article  PubMed  Google Scholar 

  24. Doney A, Fischer B, Frew D, Cumming A, Flavell DM et al (2002) Haplotype analysis of the PPARgamma Pro12Ala and C1431T variants reveals opposing associations with body weight. BMC Genet 3:21

    Article  PubMed Central  PubMed  Google Scholar 

  25. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH et al (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112:2735–2752

    Article  PubMed  Google Scholar 

  26. Gaunt TR, Rodriguez S, Day IN (2007) Cubic exact solutions for the estimation of pairwise haplotype frequencies: implications for linkage disequilibrium analyses and a web tool ‘CubeX’. BMC Bioinformatics 8:428

    Article  PubMed Central  PubMed  Google Scholar 

  27. Mirzaei H, Akrami SM, Golmohammadi T, Doosti M, Heshmat R et al (2009) Polymorphism of Pro12Ala in the peroxisome proliferator-activated receptor gamma2 gene in Iranian diabetic and obese subjects. Metab Syndr Relat Disord 7:453–458

    Article  CAS  PubMed  Google Scholar 

  28. Namvaran F, Azarpira N, Rahimi-Moghaddam P, Dabbaghmanesh MH (2011) Polymorphism of peroxisome proliferator-activated receptor gamma (PPARgamma) Pro12Ala in the Iranian population: relation with insulin resistance and response to treatment with pioglitazone in type 2 diabetes. Eur J Pharmacol 671:1–6

    Article  CAS  PubMed  Google Scholar 

  29. Meirhaeghe A, Cottel D, Amouyel P, Dallongeville J (2005) Association between peroxisome proliferator-activated receptor gamma haplotypes and the metabolic syndrome in French men and women. Diabetes 54:3043–3048

    Article  CAS  PubMed  Google Scholar 

  30. Gurnell M (2003) PPARgamma and metabolism: insights from the study of human genetic variants. Clin Endocrinol (Oxf) 59:267–277

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank all the study participants for their cooperation. This work was supported by Research Project No. 467, as a PhD thesis, financed by the Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences.

Author information

Authors and Affiliations

  1. Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hassan Rooki, Monir-sadat Haerian, Pedram Azimzadeh & Mohammad-Reza Zali

  2. Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Hassan Rooki, Reza Mirhafez & Majid Ghayour-Mobarhan

  3. Cardiovascular Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahmoud Ebrahimi & Majid Ghayour-Mobarhan

  4. Guy Hilton Research Centre, Institute for Science and Technology in Medicine, University of Keele, Thornburrow Drive, Stoke on Trent, Staffordshire, UK

    Gordon Ferns

Authors
  1. Hassan Rooki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Monir-sadat Haerian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pedram Azimzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reza Mirhafez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mahmoud Ebrahimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gordon Ferns
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Majid Ghayour-Mobarhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohammad-Reza Zali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hassan Rooki or Majid Ghayour-Mobarhan.

Additional information

Hassan Rooki and Majid Ghayour-Mobarhan have contributed equally to this study

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rooki, H., Haerian, Ms., Azimzadeh, P. et al. Associations between C1431T and Pro12Ala variants of PPARγ gene and their haplotypes with susceptibility to metabolic syndrome in an Iranian population. Mol Biol Rep 41, 3127–3133 (2014). https://doi.org/10.1007/s11033-014-3172-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3172-z

Keywords

Search

Navigation