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. 2006 Dec 5;29(7):300–304. doi: 10.1002/clc.4960290706

Association between Pro12Ala polymorphism of peroxisome proliferator‐activated receptor‐gamma 2 and myocardial infarction in the Chinese Han population

Lin Li 1, Long‐Xian Cheng 1,, Ripen Nsenga 1, Mei‐An He 2, Tang‐Chun Wu 2
PMCID: PMC6654026  PMID: 16881538

Abstract

Background: Peroxisome proliferator‐activated receptor‐gamma 2 (PPAR‐gamma 2) is a nuclear receptor that plays an important role in adipocyte differentiation, energy metabolism, and homeostasis. The Pro12Ala polymorphism of PPAR‐gamma 2 is associated with decreased risk of diabetes mellitus. Presumably, it may have a protective effect on myocardial infarction (MI).

Hypothesis: The purpose of the study was to explore the association between the Pro12Ala polymorphism and the risk of MI in the Chinese population.

Methods: The Pro12Ala polymorphism was detected by polymerase chain reaction‐restriction fragment length polymorphism among 844 subjects, including 218 patients with MI and 626 controls. Clinical parameters such as fasting serum total cholesterol, triglycerides, and plasma glucose were detected by autoanalyzer assay. Waist circumference, weight, height, and blood pressure (BP) were measured and body mass index (BMI) was calculated.

Results: The frequencies of the Ala allele in the MI and control groups were 0.053 and 0.032, respectively. There was a significant difference in genotype and allele frequency distribution between the two groups (after adjustment for age, gender, BP, fasting plasma glucose, total cholesterol, triglycerides, and smoking, odds ratio [OR] = 2.51,95% confidence interval [CI]: 1.26–5.00, p = 0.009). In the group with MI, the difference in frequency of the Ala allele in women (0.241) compared with that of men (0.056) was significant (OR = 4.29, 95% CI: 1.96–9.37, p<0.001). There was no relationship between the Pro12Ala polymorphism and waist circumference, weight, BMI, BP, or triglycerides (p>0.05).

Conclusions: Our study suggests that Pro12Ala polymorphism is associated with increased risk of MI.

Keywords: peroxisome proliferator‐activated receptor‐gamma 2, Polymorphism, myocardial infarction

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References

  • 1. Cuzzocrea S, Pisano B, Dugo L, Ianaro A, Patel NS, Di Paola R, Genovese T, Chatterjee PK, Di Rosa M, Caputi AP, Thiemermann C: Rosiglitazone and 15‐deoxy‐delta12,14‐prostaglan‐dinJ2, ligands of the peroxisome proliferator‐activated receptor‐gamma (PPAR‐gamma), reduce ischaemia/reperfusion injury of the gut. Br J Pharmacol 2003; 140 (2): 366–376 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Calnek DS, Mazzella L, Roser S, Roman J, Hart CM: Peroxisome proliferator‐activated receptor gamma ligands increase release of nitric oxide from endothelialcells. Arterioscler Thromb Vasc Biol 2003; 23 (1): 52–57 [DOI] [PubMed] [Google Scholar]
  • 3. Law RE, Goetze S, Xi XP, Jackson S, Kawano Y, Demer L, Fishbein MC, Meehan WP, Hsueh WA: Expression and function of PPARgamma in rat and human vascular smooth muscle cells. Circulation 2000; 101 (11): 1311–1318 [DOI] [PubMed] [Google Scholar]
  • 4. Hara K, Okada T, Tobe K, Yasuda K, Mori Y, Kadowaki H, Hagura R, Akanuma Y, Kimura S, Ito C, Kadowaki T: The Pro12Ala polymorphism in PPAR‐gamma 2 may confer resistance to type 2 diabetes. Biochem Biophys Res Commun 2000; 271 (1): 212–216 [DOI] [PubMed] [Google Scholar]
  • 5. Snitker S, Watanabe RM, Ani I, Xiang AH, Marroquin A, Ochoa C, Goico J, Shuldiner AR, Buchanan TA: Changes in insulin sensitivity in response to troglitazone do not differ between subjects with and without the common, functional Pro12Ala peroxisome proliferator‐activated receptor‐γ2 gene variant. Diabetes Care 2004; 27: 1365–1368 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Ridker PM, Cook NR, Cheng S, Erlich HA, Lindpaintner K, Plutzky J, Zee RY: 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 (5): 859–863 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Pischon T, Pai JK, Manson JE, Hu FB, Rexrode KM, Hunter D, Rimm EB: Peroxisome proliferator‐activated receptor‐gamma 2P12A polymorphism and risk of coronary heart disease in US men and women. Arterioscler Thromb Vasc Biol 2005; 25 (8): 1654–1658 [DOI] [PubMed] [Google Scholar]
  • 8. Schneider J, Kreuzer J, Hamann A, Nawroth PP, Dugi KA: The proline 12 alanine substitution in the peroxisome proliferator‐activated receptor‐gamma 2 gene is associated with lower lipoprotein lipase activity in vivo. Diabetes 2002; 51 (3): 867–870 [DOI] [PubMed] [Google Scholar]
  • 9. Takata N, Awata T, Inukai K, Watanabe M, Ohkubo T, Kurihara S, Inaba M, Katayama S: Pro12Ala substitution in peroxisome proliferator‐activated receptor‐gamma 2 is associated with low adiponectin concentrations in young Japanese men. Metabolism 2004; 53 (12): 1548–1551 [DOI] [PubMed] [Google Scholar]
  • 10. Simon I, Vendrell J, Gutierrez C, Fernandez‐Real JM, Vendrell I, Gallart L, Fontova R, Richart C: Pro12Ala substitution in the peroxisome proliferator‐activated receptor‐gamma is associated with increased leptin levels in women with type‐2 diabetes mellitus. Horm Res 2002; 58 (3): 143–149 [DOI] [PubMed] [Google Scholar]
  • 11. Zietz B, Barth N, Spiegel D, Schmitz G, Scholmerich J, Schaffler A: Pro12Ala polymorphism in the peroxisome proliferator‐activated receptor‐ gamma 2 (PPAR‐gamma 2) is associated with higher levels of total cholesterol and LDL‐cholesterol in male Caucasian type 2 diabetes patients. Exp Clin Endocrinol Diabetes 2002; 110 (2): 60–66 [DOI] [PubMed] [Google Scholar]
  • 12. Meirhaeghe A, Fajas L, Helbecque N, Cottel D, Auwerx J, Deeb SS, Amouyel P: Impact of the peroxisome proliferator activated receptor‐gamma 2 Pro12Ala polymorphism on adiposity, lipids and non‐insulin‐dependent diabetes mellitus. Int J Obes Relat Metab Disord 2000; 24 (2): 195–199 [DOI] [PubMed] [Google Scholar]
  • 13. Tavares V, Hirata RD, Rodrigues AC, Monte O, Salles JE, Scalissi N, Speranza AC, Hirata MH: Association between Pro12Ala polymorphism of the PPAR‐gamma2 gene and insulin sensitivity in Brazilian patients with type‐2 diabetes mellitus. Diabetes Obes Metab 2005; 7 (5): 605–611 [DOI] [PubMed] [Google Scholar]
  • 14. Memisoglu A, Hu FB, Hankinson SE, Manson JE, De Vivo I, Willett WC, Hunter DJ: Interaction between a peroxisome proliferator‐activated receptor gamma gene polymorphism and dietary fat intake in relation to body mass. Hum Mol Genet 2003; 12 (22): 2923–2929 [DOI] [PubMed] [Google Scholar]
  • 15. Yamauchi T, Kamon J, Waki H, Murakami K, Motojima K, Komeda K, Ide T, Kubota N, Terauchi Y, Tobe K, Miki H, Tsuchida A, Akanuma Y, Nagai R, Kimura S, Kadowaki T: The mechanisms by which both heterozygous peroxisome proliferator‐activated receptor‐gamma (PPAR‐gamma) deficiency and PPAR‐gamma agonists improve insulin resistance. J Biol Chem 2001; 276 (44): 41245–41254 [DOI] [PubMed] [Google Scholar]
  • 16. Yang WS, Jeng CY, Wu TJ, Tanaka S, Funahashi T, Matsuzawa Y, Wang JP, Chen CL, Tai TY, Chuang LM: Synthetic peroxisome proliferator‐activated receptor‐gamma agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care 2002; 25 (2): 376–380 [DOI] [PubMed] [Google Scholar]
  • 17. Wayman NS, Hattori Y, McDonald MC, Mota‐Filipe H, Cuzzocrea S, Pisano B, Chatterjee PK, Thiemermann C: Ligands of the peroxisome proliferator‐activated receptors (PPAR‐gamma and PPAR‐alpha) reduce myocardial infarct size. FASEB J 2002; 16 (9): 1027–1040 [DOI] [PubMed] [Google Scholar]
  • 18. Fonseca VA, Diez J, McNamara DB: Decreasing restenosis following angioplasty: The potential of peroxisome proliferator‐activated receptor gamma agonists. Diabetes Care 2004; 27 (11): 2654–2660 [DOI] [PubMed] [Google Scholar]

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