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Association between the Pro12Ala variant of the peroxisome proliferator-activated receptor-gamma2 gene and increased 24-h diastolic blood pressure in obese patients with type II diabetes

Journal of Human Hypertension volume 20, pages 684–692 (2006)Cite this article

Abstract

The aim of the study was to examine an association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR)-γ2 gene and blood pressure values assessed by 24-h ambulatory blood pressure monitoring (ABPM) in obese patients with long-lasting type II diabetes. Two hundred and fourteen obese patients (95 men and 119 women) with above 10-year history of type II diabetes were recruited for the study. In all the patients, ABPM was performed and other parameters, including age, body mass index (BMI), waist/hip ratio (WHR), haemoglobin A1c (HbA1c), serum lipids and creatinine were also evaluated. The Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism. Two subgroups of patients were compared: (a) Pro/Pro: homozygotic Pro/Pro (n=154) and (b) Ala: Ala allele carriers (Ala/Ala+Ala/Pro) (n=60). The studied groups were not different when age, BMI, WHR, HbA1c, lipids, creatinine and frequency of hypertension were compared. A similar ratio of patients from both groups were treated with angiotensin-converting enzyme inhibitors, calcium channel blockers, diuretics, β-blockers and α-blockers. A difference was observed in a mean 24-h (Ala: 71.9±8.1 vs Pro/Pro: 69.4±7.8 mm Hg, P=0.034) and a mean night time (Ala: 67.1±7.8 vs Pro/Pro: 64.5±8.4 mm Hg, P=0.025) diastolic blood pressure, which was significantly higher in patients with Ala variant. There was also a trend towards a higher mean daytime diastolic blood pressure in this group. It seems that the Pro12Ala variant is associated with an increased mean 24-h diastolic blood pressure in obese diabetic patients. Different reaction for antihypertensive medication depending on a variant of the PPAR-γ2 gene should also be considered as a possible cause of the presented results.

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References

  1. Pasceri V, Wu HD, Willerson JT, Yeh ET . Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators. Circulation 2000; 101: 235–238.

    Article  CAS  Google Scholar 

  2. Schiffrin EL, Amiri F, Benkirane K, Iglarz M, Diep QN . Peroxisome proliferator-activated receptors: vascular and cardiac effects in hypertension. Hypertension 2003; 42: 664–668.

    Article  CAS  Google Scholar 

  3. Fullert S, Schneider F, Haak E, Rau H, Badenhoop K, Lubben G et al. Effects of pioglitazone in non diabetic patients with arterial hypertension: a double-blind, placebo controlled study. J Clin Endocrinol Metab 2002; 87: 5503–5506.

    Article  CAS  Google Scholar 

  4. Konrad T, Lübben G, Franzen C . Pioglitazone lowers blood pressure in hypertensive patients with type 2 diabetes mellitus, Abstract at the ADA, 2004, 658pp.

  5. Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA et al. Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 1999; 402: 880–883.

    Article  CAS  Google Scholar 

  6. Altshuler D, Hirschhorn JN, Klannemark M, Lindgren CM, Vohl MC, Nemesh J et al. The common PPAR-γ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 2000; 26: 76–80.

    Article  CAS  Google Scholar 

  7. Douglas JA, Erdos MR . The peroxisome proliferator-activated receptor-γ2 Pro12Ala variant. Association with type 2 diabetes and trait differences. Diabetes 2001; 50: 886–890.

    Article  CAS  Google Scholar 

  8. Östgren CJ, Lindblad U, Melander O, Melander A, Groop L, Rastam L . Peroxisome proliferator-activated receptor-gammaPro12Ala polymorphism and the association with blood pressure in type 2 diabetes: skaraborg hypertension and diabetes project. J Hypertens 2003; 21: 1657–1662.

    Article  Google Scholar 

  9. O'Brien E, Mee F, Atkins N, O'Malley K . Accuracy of the SpaceLabs 90207 determined by the British Hypertension Society protocol. J Hypertens 1991; 9: 573–574.

    Article  CAS  Google Scholar 

  10. Ek J, Urhammer SA, Sorensen TIA, Andersen T, Auwerx J, Pedersen O . Homozygosity of the Pro12Ala variant of the peroxisome proliferation-activated receptor γ2 (PPAR-γ2): divergent modulating effects on body mass index in obese and lean Caucasian men. Diabetologia 1999; 42: 892–895.

    Article  CAS  Google Scholar 

  11. Yamamoto J, Kageyama S, Nemoto M, Sasaki T, Sakurai T, Ishibashi K et al. PPARgamma2 Pro12Ala polymorphism and insulin resistance in Japanese hypertensive patients. Hypertens Res 2002; 25: 25–29.

    Article  CAS  Google Scholar 

  12. Hasstedt SJ, Ren QF, Teng K, Elbein SC . Effect of the peroxisome proliferator-activated receptor-γ2 Pro12Ala variant on obesity, glucose homeostasis, and blood pressure in members of familial type 2 diabetic kindreds. J Clin Endocrinol Metab 2001; 86: 536–541.

    CAS  PubMed  Google Scholar 

  13. Sugawara A, Takeuchi K, Uruno A, Ikeda Y, Arima S, Kudo M et al. Transcriptional suppression of type 1 angiotensin II receptor gene expression by peroxisome proliferator-activated receptor-γ in vascular smooth muscle cells. Endocrinology 2001; 142: 3125–3134.

    Article  CAS  Google Scholar 

  14. Diep QN, El Mabrouk M, Cohn JS, Endemann D, Amiri F, Virdis A et al. Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: role of peroxisome proliferator-activated receptor-γ. Circulation 2002; 105: 2296–2302.

    Article  CAS  Google Scholar 

  15. Masugi J, Tamori Y, Mori H, Koike T, Kasuga M . Inhibitory effect of a proline-to-alanine substitution at codon 12 of peroxisome proliferator-activated receptor-gamma 2 on thiazolidinedione-induced adipogenesis. Biochem Biophys Res Commun 2000; 268: 178–182.

    Article  CAS  Google Scholar 

  16. Wu L, Wang R, De Champlain J, Wilson TW . Beneficial and deleterious effects of rosiglitazone on hypertension development in spontaneously hypertensive rats. Am J Hypertens 2004; 17: 749–756.

    Article  CAS  Google Scholar 

  17. Brown CD, Higgins M, Donato KA, Rohde FC, Garrison R, Obarzanek E et al. Body mass index and the prevalence of hypertension and dyslipidemia. Obes Res 2000; 8: 605–619.

    Article  CAS  Google Scholar 

  18. Fekete T, Levi L, Teszler A . Arterial hypertension in diabetic patients. Role of obesity. Med Intern 1983; 21: 273–278.

    CAS  Google Scholar 

  19. Bo S, Gentile L, Cavallo-Perin P, Vineis P, Ghia V . Sex- and BMI-related differences in risk factors for coronary artery disease in patients with type 2 diabetes mellitus. Acta Diabetol 1999; 36: 147–153.

    Article  CAS  Google Scholar 

  20. Swarbrick MM, Chapman CM, McQuillan BM, Hung J, Thompson PL, Beilby JP . A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor-gamma 2 is associated with combined hyperlipidaemia in obesity. Eur J Endocrinol 2001; 144: 277–282.

    Article  CAS  Google Scholar 

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Acknowledgements

The study was supported by Polish Scientific Research Committee – Grant no. 6P05B05020.

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Authors and Affiliations

  1. Department of Endocrinology, Hypertension and Metabolic Diseases, Pomeranian Medical University, Szczecin, Poland

    A Stefański, L Majkowska, M Frankow, P Moleda & K Pilarska

  2. Department of Clinical Biochemistry and Laboratory Diagnostics, Pomeranian Medical University, Szczecin, Poland

    A Ciechanowicz & M Parczewski

  3. Department of Biochemistry, Pomeranian Medical University, Szczecin, Poland

    K Safranow

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  1. A Stefański
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Correspondence to A Stefański.

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Stefański, A., Majkowska, L., Ciechanowicz, A. et al. Association between the Pro12Ala variant of the peroxisome proliferator-activated receptor-gamma2 gene and increased 24-h diastolic blood pressure in obese patients with type II diabetes. J Hum Hypertens 20, 684–692 (2006). https://doi.org/10.1038/sj.jhh.1002040

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