Skip to main content

Advertisement

SpringerLink
Log in

Association of Pro12Ala (rs1801282) variant of PPAR gamma with Rheumatoid Arthritis in a Pakistani population

  • Short Communication
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) belongs to a receptor superfamily of ligand-activated transcription factors, encoded by PPARG gene. Role of PPARγ has been well established in variety of metabolic disorders and in regulation of inflammation. In the present study, we aimed to investigate the association of PPARG (Pro12Ala; rs1801282) in clinically definite Pakistani Rheumatoid Arthritis (RA) patients and matching controls. The genotypes of the Pro12Ala variant in the PPARG were determined in a sample of 300 Pakistanis, including 150 RA cases and 150 controls. The genotyping was performed using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) method, and the data was analyzed through Graphpad Prism 5 V software. Allele-specific primer set (two forward: PPARG-F1, PPARG-F2 and a common reverse primer: PPARG-R) was used for amplification, and the product was resolved on 2 % agarose gel. The CC (ProPro) genotype has higher frequency in controls than RA cases [75 (50.0 %) vs. 51 (34.0 %)], whereas the CG (ProAla) genotype has relatively same frequencies in both cases and controls [72 (48.0 %) vs. 70 (46.6 %)]. However, significantly higher frequency of GG (AlaAla) genotype was observed in cases [27 (18.0 %) vs. 5 (3.3 %); χ2 18.54; p < 0.0001]. Furthermore, the minor allele G has significantly higher allele frequency in cases having same trend and direction of association (OR 1.991(1.412–2.808); p < 0.0001). These observations suggest that Pro12Ala (rs1801282), a coding variant in the PPARG gene, is associated with Rheumatoid Arthritis in Pakistanis.

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

Fig. 1
Fig. 2

References

  1. Seldin MF, Amos CI, Ward R, Gregersen PK (1999) The genetics evolution and the assault on Rheumatoid Arthritis. Arthritis Rheum 42:1071–1079

    Article  PubMed  CAS  Google Scholar 

  2. MacGregor AJ, Snieder H, Rigby AS, Koskenvuo M, Kaprio J, Kaprio J et al (2000) Characterizing the quantitative genetic contribution to Rheumatoid Arthritis using data from twins. Arthritis Rheum 43:30–37

    Article  PubMed  CAS  Google Scholar 

  3. Firestein GS (2003) Evolving concepts of Rheumatoid Arthritis. Nature 423:356–361

    Article  PubMed  CAS  Google Scholar 

  4. Kersten S, Desvergne B, Wahli W (2000) Roles of PPARs in health and disease. Nature 405:421–424

    Article  PubMed  CAS  Google Scholar 

  5. Hara K, Okada T, Tobe K, Yasuda K, Mori Y, Kadowaki T et al (2000) The Pro12Ala polymorphism in PPAR gamma2 may confer resistance to type 2 diabetes. Biochem Biophys Res Commun 271:212–216

    Article  PubMed  CAS  Google Scholar 

  6. Frederiksen L, Brødbaek K, Fenger M, Jørgensen T, Borch-Johnsen K et al (2002) Comment: studies of the Pro12Ala polymorphism of the PPAR-gamma gene in the Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome. J Clin Endocrinol Metab 87:3989–3992

    PubMed  CAS  Google Scholar 

  7. Su CG, Wen X, Bailey ST, Jiang W, Rangwala SM, Keilbaugh SA et al (1999) A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response. J Clin Invest 104:383–389

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Desreumaux P, Dubuquoy L, Nutten S, Peuchmaur M, Englaro W, Schoonjans K et al (2001) Attenuation of colon inflammation through activation of the retinoid X receptor (RXR)/peroxisome proliferators- activated receptor gamma (PPAR-gamma) heterodimer. A basis for new therapeutic strategies. J Exp Med 193:827–838

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  9. Gupta RA, Dubois RN (2002) Controversy: PPAR gamma as a target for treatment of colorectal cancer. Am J Physiol Gastrointest Liver Physiol 283:266–269

    Google Scholar 

  10. Debril MB, Renaud JP, Fajas L, Auwerx J (2001) The pleitropic functions of peroxisome proliferator5 activated receptor gamma. J Mol Med 79:30–47

    Article  PubMed  CAS  Google Scholar 

  11. Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR (2003) Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR5gamma ligand rosiglitazone. Hepatology 38:1008–1017

    Article  PubMed  CAS  Google Scholar 

  12. Lewis JD, Lichtenstein GR, Deren JJ, Sands BE, Hanauer SB, Katz JA et al (2008) Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial. Gastroenterology 134:688–695

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  13. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of Rheumatoid Arthritis. Arthritis Rheum 31:315–324

    Article  PubMed  CAS  Google Scholar 

  14. Yamauchi T, Kamon J, Waki H, Murakami K, Motojima K, Komeda K et al (2001) The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance. J Biol Chem 276(44):41245–41254

    Article  PubMed  CAS  Google Scholar 

  15. Michalik L, Auwerx J, Berger JP, Chatterjee VK, Glass CK, Gonzalez FJ et al (2006) International union of pharmacology. Peroxisome proliferator-activated receptors. Pharmacol Rev 58(4):726–741

    Article  PubMed  CAS  Google Scholar 

  16. Stumvoll M, Haring H (2002) The peroxisome proliferator-activated receptor gamma2 Pro12Ala polymorphism. Diabetes 51:2341–2347

    Article  PubMed  CAS  Google Scholar 

  17. Doney AS, Fischer B, Cecil JE, Boylan K, McGuigan FE, Ralston SH 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  PubMed  CAS  Google Scholar 

  18. Al-Shali KZ, House AA, Hanley AJ, Khan HM, Harris SB, Zinman B et al (2004) Genetic variation in PPARG encoding peroxisome proliferator-activated receptor gamma associated with carotid atherosclerosis. Stroke 35:2036–2040

    Article  PubMed  CAS  Google Scholar 

  19. Temelkova-Kurktschiev T, Hanefeld M, Chinetti G, Zawadzki C, Haulon S, Kubaszek A, Koehler C et al (2004) Ala12Ala genotype of the peroxisome proliferator 5 activated receptor gamma2 protects against atherosclerosis. J Clin Endocrinol Metab 89:4238–4242

    Article  PubMed  CAS  Google Scholar 

  20. Herrmann SM, Ringel J, Wang JG, Staessen JA, Brand E et al (2002) Peroxisome proliferator activated receptor gamma polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes: the Berlin Diabetes Mellitus (BeDiaM) study. Diabetes 51:2653–2657

    Article  PubMed  CAS  Google Scholar 

  21. Wu Z, Lou Y, Jin W, Liu Y, Lu L, Lu G (2012) The Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma-2 gene (PPARγ2) is associated with increased risk of coronary artery disease: a meta-analysis. PLoS ONE 7(12):e53105

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. Pan XF, Song XB, Wang LL, Li LX, Ying BW (2009) Association of the Pro12Ala polymorphism in peroxisome proliferators activated receptor-gamma gene with Rheumatoid Arthritis in Sichuan Province of China. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 26(1):87–90

    PubMed  CAS  Google Scholar 

  23. Klotz L, Schmidt S, Heun R, Klockgether T, Kölsch H (2009) Association of the PPARγ gene polymorphism Pro12Ala with delayed onset of multiple sclerosis. Neurosci Lett 449:81–83

    Article  PubMed  CAS  Google Scholar 

  24. El-Sohemy A, Cornelis MC, Park YW, Bae SC (2006) Catalase and PPARgamma2 genotype and risk of Rheumatoid Arthritis in Koreans. Rheumatol Int 26(5):388–392

    Article  PubMed  CAS  Google Scholar 

  25. Deeb SS, Fajas L, Nemoto M, Pihlajamaki J, Mykkanen L, Kuusisto J, Laakso M 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  PubMed  CAS  Google Scholar 

  26. Masugi J, Tamori Y, Mori H, Koike T, Kasuga M et al (2000) Inhibitory effect of a prolineto-alanine substitution at codon 12 of peroxisome proliferator-activated receptor gamma on thiazolidinedione-induced adipogenesis. Biochem Biophys Res Commun 268:178–182

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by Higher Education Commission (HEC) of Pakistan. We are thankful to patients and other healthy control individuals for their cooperation and participation in the study.

Conflict of interest

Authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology (NUST), Islamabad, 44000, Pakistan

    Syed Fazal Jalil, Iltaf Ahmed, Zeeshan Gauhar, Peter John & Attya Bhatti

  2. Rheumatology Unit Military Hospital Rawalpindi, Rawalpindi, Pakistan

    Mushtaq Ahmed

  3. Rahmat Noor Clinic and Arthritis Research Center Rawalpindi, Rawalpindi, Pakistan

    Javaid M. Malik

Authors
  1. Syed Fazal Jalil
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Iltaf Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zeeshan Gauhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mushtaq Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Javaid M. Malik
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peter John
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Attya Bhatti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Syed Fazal Jalil.

Additional information

I. Ahmed and S. F. Jalil equally contributed and are both first authors of this manuscript.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jalil, S.F., Ahmed, I., Gauhar, Z. et al. Association of Pro12Ala (rs1801282) variant of PPAR gamma with Rheumatoid Arthritis in a Pakistani population. Rheumatol Int 34, 699–703 (2014). https://doi.org/10.1007/s00296-013-2768-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-013-2768-2

Keywords

Search

Navigation