Archives of Medical Research
Volume 37, Issue 6 , Pages 736-743 , August 2006

Lack of Association between the Pro12Ala Polymorphism in PPAR-γ2 Gene and Body Weight Changes, Insulin Resistance and Chronic Diabetic Complications in Obese Patients with Type 2 Diabetes

  • Adam Stefanski

      Affiliations

    • Department of Endocrinology, Hypertension and Metabolic Diseases, Pomeranian Medical University, Szczecin, Poland
    • Corresponding Author InformationAddress reprint requests to: Dr. Adam Stefanski, Department of Endocrinology, Hypertension and Metabolic Diseases, Pomeranian Medical University, ul. Arkonska 4, 71-455 Szczecin, Poland
    • ,
  • Liliana Majkowska

      Affiliations

    • Department of Endocrinology, Hypertension and Metabolic Diseases, Pomeranian Medical University, Szczecin, Poland
    • ,
  • Andrzej Ciechanowicz

      Affiliations

    • Department of Clinical Biochemistry and Laboratory Diagnostics, Pomeranian Medical University, Szczecin, Poland
    • ,
  • Miroslaw Frankow

      Affiliations

    • Department of Endocrinology, Hypertension and Metabolic Diseases, Pomeranian Medical University, Szczecin, Poland
    • ,
  • Krzysztof Safranow

      Affiliations

    • Department of Biochemistry, Pomeranian Medical University, Szczecin, Poland
    • ,
  • Milosz Parczewski

      Affiliations

    • Department of Clinical Biochemistry and Laboratory Diagnostics, Pomeranian Medical University, Szczecin, Poland
    • ,
  • Krystyna Pilarska

      Affiliations

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

Received 24 July 2005 ,Accepted 9 January 2006.

References 

  1. De Fronzo RA. Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev. 1997;5:177–285
  2. Rieusset J, Andreelli F, Auboeuf D, Roques M, Vallier P, Riou JP, et al. Insulin acutely regulates the expression of the peroxisome proliferator-activated receptor-gamma in human adipocytes. Diabetes. 1999;48:699–705
  3. Fajas L, Auboeuf D, Raspe E, Schoonjans K, Lefebvre AM, Saladin R, et al. Organization, promoter analysis and expression of the human PPARγ gene. J Biol Chem. 1997;272:18779–18789
  4. Fajas L, Fruchart JC, Auwerx J. PPARγ3 mRNA; a distinct PPARγ mRNA subtype transcribed from an independent promoter. FEBS Lett. 1998;438:55–60
  5. Werman A, Hollenberg A, Solanes G, Bjorbaek C, Vidal-Puig AJ, Flier JS. Ligand-independent activation domain in the N terminus of peroxisome proliferator-activated receptor gamma (PPAR gamma). Differential activity of PPAR gamma-1 and -2 isoforms and influence of insulin. J Biol Chem. 1998;272:20230–20235
  6. Yen CJ, Beamer BA, Negri C, Silver K, Brown KA, Yarnall DP, et al. Molecular scanning of the human peroxisome proliferator-activated receptor γ (PPARγ) gene in diabetic Caucasians: identification of a Prol12Ala PPAR γ2 missense mutation. Biochem Biophys Res Commun. 1997;240:270–274
  7. Altshuler D, Hirschhorn JN, Klannemark M, Lindgren CM, Vohl MC, Nemesh J, et al. The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet. 2000;26:76–80
  8. Deeb S, Fajas L, Nemoto M, Laakso M, Fujimoto W, Auwerx J. A Pro12 Ala substitution in the human peroxisome proliferator-activated receptor gamma2 is associated with decreased receptor activity, improved insulin sensitivity, and lowered body mass index. Nat Genet. 1998;20:284–287
  9. Koch M, Rett K, Maerker E, Volk A, Haist K, Deninger M, et al. The PPARγ2 amino acid polymorphism Pro 12 Ala is prevalent in offspring of type 2 diabetic patients and is associated to increased insulin sensitivity in a subgroup of obese subjects. Diabetologia. 1999;42:758–762
  10. Beamer BA, Yen CJ, Andersen RE, Muller D, Elahi D, Cheskin LJ, et al. Association of the Pro12Ala variant in peroxisome proliferator-activated receptor gamma2 gene with obesity in two Caucasian populations. Diabetes. 1998;47:1806–1808
  11. 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
  12. Gurnell M, Savage DB, Chatterjee VKK, O'Rahilly S. The metabolic syndrome: peroxisome proliferator-activated receptor γ and its therapeutic modulation. J Clin Endocrinol Metab. 2003;88:2412–2421
  13. Hara K, Okada T, Tobe K, Yasuda K, Mori Y, Kadowaki H, et al. The Pro12Ala polymorphism in PPAR-gamma2 may confer resistance to type 2 diabetes. Biochem Biophys Res Commun. 2000;271:212–216
  14. Jacob S, Stumvoll M, Becker R, Koch M, Nielsen M, Loblein K, et al. The PPARgamma2 polymorphism Pro12Ala is associated with better insulin sensitivity in the offspring of type 2 diabetic patients. Horm Metab Res. 2000;32:413–416
  15. Ek J, Andersen G, Urhammer SA, Hansen LA, Carstensen B, Borch-Johnsen K, et al. Studies of the Pro12Ala polymorphism of the perioxisome proliferator-activated receptor-γ2 (PPAR-γ2) gene in relation to insulin sensitivity among glucose tolerant Caucasians. Diabetologia. 2001;44:1170–1176
  16. Delerive P, Martin-Nizard F, Chinetti G, Trottein F, Fruchart JC, Najib J, et al. Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway. Circ Res. 1999;85:394–402
  17. Temelkova-Kurktschiev T, Hanefeld M, Chinetti G, Zawadzki C, Haulon S, Kubaszek A, et al. Ala12Ala genotype of the peroxisome proliferator-activated receptor-γ 2 protects against atherosclerosis. J Clin Endocrinol Metab. 2004;89:4238–4242
  18. Ridker PM, Cook NR, Cheng S, Erlich HA, Lindpaintner K, Plutzky J, et al. Alanine for proline substitution in the peroxisome proliferator-activated receptor gamma-2 (PPARG2) gene and the risk of incident myocardial infarction. Arterioscler Thromb Vasc Biol. 2003;23:859–863
  19. Caramori ML, Canani LH, Costa LA, Gross JL. The human peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is associated with decreased risk of diabetic nephropathy in patients with type 2 diabetes. Diabetes. 2003;52:3010–3013
  20. Herrmann SM, Ringel J, Wang JG, Staessen JA, Brand E. Berlin Diabetes Mellitus (BeDiaM) Study. Peroxisome proliferator-activated receptor-gamma2 polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes: The Berlin Diabetes Mellitus (BeDiaM) Study. Diabetes. 2002;51:2653–2657
  21. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27:1487–1495
  22. Malecki MT, Frey J, Klupa T, Skupien J, Walus M, Mlynarski W, et al. The Pro12Ala polymorphism of PPARgamma2 gene and susceptibility to type 2 diabetes mellitus in a Polish population. Diabetes Res Clin Pract. 2003;62:105–111
  23. Pihlajamaki J, Vanhala M, Vanhala P, Laakso M. The Pro12Ala polymorphism of the PPAR gamma 2 gene regulates weight from birth to adulthood. Obes Res. 2004;12:187–190
  24. Kao WH, Coresh J, Shuldiner AR, Boerwinkle E, Bray MS, Brancati FL. Atherosclerosis Risk in Communities Study. 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. 2003;52:1568–1572
  25. 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
  26. Makimattila S, Nikkila K, Yki-Jarvinen H. Causes of weight gain during insulin therapy with and without metformin in patients with type II diabetes mellitus. Diabetologia. 1999;42:406–412
  27. Wolever TM, Chiasson JL, Josse RG, Hunt JA, Palmason C, Rodger NW, et al. Small weight loss on long-term acarbose therapy with no change in dietary pattern or nutrient intake of individuals with non-insulin-dependent diabetes. Int J Obes Relat Metab Disord. 1997;21:756–763
  28. Parulkar AA, Pendergrass ML, Granda-Ayala R, Lee TR, Fonseca VA. Nonhypoglycemic effects of thiazolidinediones. Ann Intern Med. 2001;134:61–71
  29. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–853
  30. 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
  31. Bluher M, Paschke R. Analysis of the relationship between PPAR-gamma 2 gene variants and severe insulin resistance in obese patients with impaired glucose. Exp Clin Endocrinol Diabetes. 2003;111:85–90
  32. Rosmond R, Chagnon M, Bouchard C. The Pro12Ala PPARgamma2 gene missense mutation is associated with obesity and insulin resistance in Swedish middle-aged men. Diabetes Metab Res Rev. 2003;19:159–163
  33. Li S, Chen W, Srinivasan SR, Boerwinkle E, Berenson GS. The Bogalusa Heart Study. The peroxisome proliferator-activated receptor-gamma2 gene polymorphism (Pro12Ala) beneficially influences insulin resistance and its tracking from childhood to adulthood: the Bogalusa Heart Study. Diabetes. 2003;52:1265–1269
  34. Kahara T, Takamura T, Hayakawa T, Nagai Y, Yamaguchi H, Katsuki T, et al. PPARgamma gene polymorphism is associated with exercise-mediated changes of insulin resistance in healthy men. Metabolism. 2003;52:209–212
  35. Ostergard T, Ek J, Hamid Y, Saltin B, Pedersen OB, Hansen T, et al. Influence of the PPAR-gamma2 Pro12Ala and ACE I/D polymorphisms on insulin sensitivity and training effects in healthy offspring of type 2 diabetic subjects. Horm Metab Res. 2005;37(2):99–105
  36. Lindi VI, Uusitupa MI, Lindstrom J, Louheranta A, Eriksson JG, Valle TT, et al. Finnish Diabetes Prevention Study. Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study. Diabetes. 2002;51(8):2581–2586
  37. Guan Y, Zhang Y, Schneider A, Davis L, Breyer RM, Breyer MD. Peroxisome proliferator-activated receptor-gamma activity is associated with renal microvasculature. Am J Physiol Renal Physiol. 2001;281:F1036–F1046
  38. Asano T, Wakisaka M, Yoshinari M, Iino K, Sonoki K, Iwase M, et al. Peroxisome proliferator-activated receptor gamma1 (PPARgamma1) expresses in rat mesangial cells and PPARgamma agonists modulate its differentiation. Biochim Biophys Acta. 2000;1497:148–154
  39. Iijima K, Yoshizumi M, Ako J, Eto M, Kim S, Hashimoto M, et al. Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in rat aortic smooth muscle cells. Biochem Biophys Res Commun. 1998;247:353–356
  40. Florez JC. Phenotypic consequences of the peroxisome proliferator-activated receptor-gamma Pro12Ala polymorphism: the weight of the evidence in genetic association studies. J Clin Endocrinol Metab. 2004;89:4234–4237

PII: S0188-4409(06)00092-0

doi: 10.1016/j.arcmed.2006.01.009

Archives of Medical Research
Volume 37, Issue 6 , Pages 736-743 , August 2006

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