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Association of peroxisome proliferator-activated receptorγ gene Pro12Ala and C161T polymorphisms with cardiovascular risk factors in maintenance hemodialysis patients

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Abstract

The Pro12Ala and C161T polymorphisms in peroxisome proliferator-activated receptor γ (PPARγ) have been shown to be associated with carotid artery atherosclerosis. It remains unclear whether these two polymorphisms are associated with risk factors for cardiovascular disease (CVD) in hemodialysis (HD) patients. Therefore, the PPARγ genotypes in 99 HD patients and 149 controls were determined, and clinical characteristics among the different genotypes were compared. We found that the frequency of the Pro12Ala and C161T polymorphisms in HD patients was similar to that in healthy controls, but C161T polymorphism and T allele frequencies in HD patients with CVD were lower than that in HD patients without CVD. Carotid artery plaque (CAP) and carotid intima-media thickness (CIMT) in HD patients with CT + TT or Pro12Ala genotypes were also less than that in patients with CCor Pro12Pro genotypes, respectively. HD patients with CT + TT genotype had lower serum C reactive protein (CRP) levels, as well as higher triceps skin fold (TSF) thickness, mid arm circumference (MAC) and mean mid arm circumference (MMAC) than HD patients with CC genotype (P < 0.05). Moreover, CIMT of the Pro12Ala-CT161 subgroup was less than the Pro12Pro-CC161 and Pro12Pro-CT161 subgroup, and, CAP amounts of the Pro12Ala-CT161 subgroup was less than the Pro12Pro-CC161 subgroup. Our results indicate that the Pro12Ala and C161T polymorphisms were associated with some important risk factors for CVD in HD patients in the Han Chinese population.

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References

  1. Kliewer SA, Willson TM (1998) The nuclear receptor PPARgamma-bigger than fat. Curr Opin Genet 8:576–581

    Article  CAS  Google Scholar 

  2. Vidal-Puig AJ, Considine RV, Jimenez-Linan M (1997) Peroxisome proliferator activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulatin by insulin and glucocorticoids. J Clin Invest 99:2416–2422

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  3. Haraguchi G, Kobayashi Y, Brown ML, Tanaka A, Isobe M, Gianturco SH, Bradley WA (2003) PPAR (alpha) and PPAR (gamma) activators suppress the monocyte- macrophage apoB-48 receptor. J Lipid Res 44:1224–1231

    Article  PubMed  CAS  Google Scholar 

  4. Dumasia R, Eagle KA, Kline-Rogers E, May N, Cho L, Mukherjee D (2005) Role of PPAR-gamma agonist thiazolidinediones in treatment of pre-diabetic and diabetic individuals: a cardiovascular perspective. Curr Drug Targets Cardiovasc Haematol Disord 5:377–386

    Article  PubMed  CAS  Google Scholar 

  5. Bishop-Bailey D (2000) Peroxisome proliferator-activated receptors in the cardiovascular system. Br J Pharmacol 129:823–834

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Paracchini V, Pedotti P, Taioli E (2005) Genetics of leptin and obesity: a HuGE review. Am J Epidemiol 162:101–114

    Article  PubMed  Google Scholar 

  7. Werman A, Hollenberg A, Solanes G, Bjorbaek C, Vidal-Puig AJ, Flier JS (1997) Ligand-independent activation domain in the N terminus of peroxisome proliferator-activated receptor gamma (PPARgamma). Differential activity of PPARgamma1 and -2 isoforms and influence of insulin. J Biol Chem 272:20230–20235

    Article  PubMed  CAS  Google Scholar 

  8. Mori H, Ikegami H, Kawaguchi Y et al (2001) The Pro12 → Ala substitution in PPAR-γ is associated with resistance to development of diabetes in the general population: possible involvement in impairment of insulin secretion in individuals with type 2 diabetes. Diabetes 50(4):891–894

    Article  PubMed  CAS  Google Scholar 

  9. Ghoussaini M, Meyre D, Lobbens S et al (2005) Implication of the Pro12Ala polymorphism of the PPAR-gamma2 gene in type 2 diabetes and obesity in the French population. BMC Medical Genetics 6:article 11

    Article  Google Scholar 

  10. Chao TH, Li YH, Chen JH, Wu HL, Shi GY, Liu PY, Tsai WC, Guo HR (2004) The 161TT genotype in the exon 6 of the peroxisome-proliferator-activated receptor gamma gene is associated with premature acute myocardial infarction and increased lipid peroxidation in habitual heavy smokers. Clin Sci (Lond) 107:461–466

    Article  CAS  Google Scholar 

  11. Wang XL, Oosterhof J, Duarte N (1999) Peroxisome proliferator-activated receptor gamma C161T polymorphism and coronary artery disease. Cardiovasc Res 44:588–594

    Article  PubMed  CAS  Google Scholar 

  12. Szeto CC, Chow KM, Poon PY, Kwan BC, Li PK (2008) Peroxisome proliferator-activated receptor-gamma gene polymorphism and risk of cardiovascular disease in patients with diabetic nephropathy. Am J Nephrol 28:715–722

    Article  PubMed  CAS  Google Scholar 

  13. Wan J, Xiong S, Chao S, Xiao J, Ma Y, Wang J, Roy S (2010) PPARγ gene C161T substitution alters lipid profile in Chinese patients with coronary artery disease and type 2 diabetes mellitus. Cardiovasc Diabetol 24:9–13

    Google Scholar 

  14. Ereqat S, Nasereddin A, Azmi K, Abdeen Z, Amin R (2009) Impact of the Pro12Ala polymorphism of the PPAR-Gamma 2 gene on metabolic and clinicalcharacteristics in the Palestinian type 2 diabetic patients. PPAR Res 2009:874126

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Vogel U, Segel S, Dethlefsen C, Tjønneland A, Saber AT, Wallin H, Jensen MK, Schmidt EB, Andersen PS, Overvad K (2009) PPARγ Pro12Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes. BMC Med Genet 10:52

    Article  PubMed  PubMed Central  Google Scholar 

  16. Zafarmand MH, van der Schouw YT, Grobbee DE, de Leeuw PW, Bots ML (2008) Peroxisome proliferator-activated receptor gamma-2 P12A polymorphism and risk of acute myocardial infarction, coronary heart disease and ischemic stroke: a case-cohort study and meta-analyses. Vasc Health Risk Manag 4(2):427–436

    PubMed  CAS  PubMed Central  Google Scholar 

  17. 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  CAS  PubMed Central  Google Scholar 

  18. Xu W, Xu J, Sun B, Chen H, Wang Y, Huang F, Xi P, Jiang J (2013) The effect of PPARG gene polymorphisms on the risk of coronary heart disease: a meta-analysis. Mol Biol Rep 40(2):875–884

    Article  PubMed  CAS  Google Scholar 

  19. Ding S, Liu L, Zhuge QC, Yu Z, Zhang X, Xie J, Hong W, Wang S, Yang Y, Chen B (2012) The meta-analysis of the association of PPARG P12A, C161T polymorphism and coronary heart disease. Wien Klin Wochenschr 124(19–20):671–677

    Article  PubMed  CAS  Google Scholar 

  20. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D et al (2000) Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 342:1478–1483

    Article  PubMed  CAS  Google Scholar 

  21. Efstratiadis G, Tziomalos K, Mikhailidis DP, Athyros VG, Hatzitolios A (2008) Atherogenesis in renal patients: a model of vascular disease? Curr Vasc Pharmacol 6:93–107

    Article  PubMed  CAS  Google Scholar 

  22. NKF-DOQI (2001) Clinical Practice Guidelines for Hemodialysis Adequacy v. Hemodialysis dose troubleshooting. Am J Kidney Dis 37:542

  23. Kao WH, Coresh J, Shuldiner AR, Boerwinkle E, Bray MS, Brancati FL (2003) Pro12Ala of the peroxisome proliferator-activated receptor gamma2 gene is associated with lower serum insulin levels in nonobese African-Americans: the atherosclerosis risk in communities study. Diabetes 52:1568–1572

    Article  PubMed  CAS  Google Scholar 

  24. Radha V, Vimaleswaran KS, Babu HN, Abate N, Chandalia M, Satija P, Grundy SM, Ghosh S, Majumder PP, Deepa R, Rao SM, Mohan V (2006) Role of genetic polymorphism peroxisome proliferator-activated receptor-gamma2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: evidence for heterogeneity. Diabetes Care 29:1046–1051

    Article  PubMed  CAS  Google Scholar 

  25. Franck N, Länne T, Astrand O, Engvall J, Lindström T, Ostgren CJ, Nystrom FH (2012) Cardiovascular risk factors related to the PPAR γ Pro12Ala polymorphism in patients with type 2 diabetes are gender dependent. Blood Press 21(2):122–127

    Article  PubMed  CAS  Google Scholar 

  26. Yilmaz-Aydogan H, Kurnaz O, Kurt O, Akadam-Teker B, Kucukhuseyin O, Tekeli A, Isbir T (2011) Effects of the PPARG P12A and C161T gene variants on serum lipids in coronary heart disease patients with and without Type 2 diabetes. Mol Cell Biochem 358:355–363

    Article  PubMed  CAS  Google Scholar 

  27. Wu Z, Lou Y, Jin W (2013) The C161T polymorphism in the peroxisome proliferator-activated receptor gamma gene (PPARc) is associated with risk of coronary artery disease: a meta-analysis. Mol Biol Rep 40:3101–3112

    Article  PubMed  CAS  Google Scholar 

  28. Yki-Jarvinen H (2004) Thiazolidinediones. N Engl J Med 351:1106–1118

    Article  PubMed  Google Scholar 

  29. Wang N, Yin R, Liu Y, Mao G, Xi F (2011) Role of peroxisome proliferator activated receptor-gamma in atherosclerosis: an update. Circ J 75:528–535

    Article  PubMed  CAS  Google Scholar 

  30. Huang W, Andras IE, Rha GB, Hennig B, Toborek M (2011) PPARalpha and PPARgamma protect against HIV-1-induced MMP-9 overexpression via caveolae-associated ERK and Akt signaling. FASEB J 25:3979–3988

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Morishige K, Shimokawa H, Matsumoto Y et al (2003) Overexpression of matrix metelloproteinase-9 promotes intravascular thrombus formation in porcine coronary arteries in vivo. Cardiovasc Res 57:572–585

    Article  PubMed  CAS  Google Scholar 

  32. Iwata E, Yamamoto I, Motomura T, Tsubakimori S, Nohnen S, Ohmoto M, Igarashi T, Azuma J (2003) The association of Pro12Ala polymorphism in PPARgamma2 with lower carotid artery IMT in Japanese. Diabetes Res Clin Pract 62(1):55–59

    Article  PubMed  CAS  Google Scholar 

  33. Webb DR, Davies MJ, Gray LJ, Abrams KR, Srinivasan B, Das S, Taub N, Lawrence I, Sutton S, Khunti K (2010) Searching for the right outcome? A systematic review and meta-analysis of controlled trials using carotid intima-media thickness or pulse wave velocity to infer antiatherogenic properties of thiazolidinediones. Diabetes Obes Metab 12(2):124–132

    Article  PubMed  CAS  Google Scholar 

  34. Kalaitzidis RG, Sarafidis PA, Bakris GL (2009) Effects of thiazolidinediones beyond glycaemic control. Curr Pharm Des 15(5):529–536

    Article  PubMed  CAS  Google Scholar 

  35. Bhatt DL, Chew DP, Grines C, Mukherjee D, Leesar M et al (2007) Peroxisome proliferator-activated receptor γ agonists for the prevention of adverse events following percutaneous coronary revascularization-results of the PPAR study. Am Heart J 154(1):137–143

    Article  PubMed  CAS  Google Scholar 

  36. Liu Y, Yuan Z, Liu Y, Zhang J, Yin P, Wang D, Wang Y, Kishimoto C, Ma A (2007) PPARgamma gene C161T substitution is associated with reduced risk of coronary artery disease and decreased proinflammatory cytokine expression. Am Heart J 154(4):718–724

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This project was supported by Shanghai Pudong New District Key Department Grant (PWZxk2010-02).

Conflict of interest

The authors have declared that no competing interests exist.

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Authors and Affiliations

  1. Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, Jimo Road 150, Shanghai, 200120, China

    Feng Liu, Yingying Zhang, Hualin Qi, Jun Wang, Yi Wang, Wei Jiang, Xintian Zhang, Haidong Yan & Shougang Zhuang

  2. Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai, Changhai Road 168, Shanghai, 200433, China

    Xiaobin Mei

  3. Alpert Medical School of Brown University Rhode Island Hospital, Middle House 301, 593 Eddy Street, Providence, RI, 02903, USA

    Shougang Zhuang

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  1. Feng Liu
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  2. Xiaobin Mei
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Correspondence to Shougang Zhuang.

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Feng Liu, Xiaobin Mei contributed equally to this work.

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Liu, F., Mei, X., Zhang, Y. et al. Association of peroxisome proliferator-activated receptorγ gene Pro12Ala and C161T polymorphisms with cardiovascular risk factors in maintenance hemodialysis patients. Mol Biol Rep 41, 7555–7565 (2014). https://doi.org/10.1007/s11033-014-3645-0

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