Case-control study on peroxisome proliferator-activated receptor gamma polymorphism and interaction with HDL on essential hypertension in Chinese Han

Document Type : Original Article


1 Department of Cardiac Surgery, The affiliated Hospital of Qingdao University, Qingdao 266003, China

2 Department of Cardiac Surgery, Beijing Fuwai Hospital, Beijing 100037, China

3 Department of Cardiac Surgery, Qingdao Fuwai Hospital, Qingdao 266034, China


Objective(s): To investigate the association of single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors gamma (PPARG) with essential hypertension (EH) and additional role of gene– high-density lipoprotein cholesterol (HDL) interaction.
Materials and Methods:A total of 1640 patients with EH (806 males, 834 females), with a mean age of 52.5±12.6 years, were selected, including 816 EH patients and 824 controls, who were enrolled from the community. Three SNPs were selected for genotyping in the case–control study: rs10865710, rs709158, rs1805192. Logistic regression model was used to examine the interaction between SNP and HDL on EH, odds ratio (OR) and 95% confidence interval (95% CI) were also calculated.
Results: All genotypes were distributed according to Hardy–Weinberg equilibrium in controls. Logistic regression analysis showed an association between genotypes of variants in rs1805192 and decreased EH risk, EH risk was significantly lower in carriers of Ala allele of the rs1805192 polymorphism than those with Pro/Pro (Pro/Ala+ Ala/Ala versus Pro/Pro, adjusted OR (95% CI) =0.65 (0.53–0.83), after covariate adjustment. In addition, the Ala allele of the rs1805192 polymorphism was also associated with diastolic blood pressure (DBP), but not systolic blood pressure (SBP), we also found, by interaction analysis, combined effect of rs1805192 and HDL on EH risk after covariate adjustment.
Conclusion: Our results support an important association between rs1805192 minor allele (Ala allele) of PPARG and lower EH risk, the interaction analysis showed a combined effect of Ala- HDL on lower EH risk.


1. Yagil Y, Yagil C. The search for the genetic basis of hypertension. Curr Opin Nephrol Hypertens 2005; 14:141–147.
2. Halperin RO, Sesso HD, Ma J, Buring JE, Stampfer MJ, Gaziano JM. Dyslipidemia and the risk of incident hypertension in men. Hypertension 2006; 47:45-50. 
3. Guo ZR, Hu XS, Wu M, Zhou MH, Zhou ZY. A prospective study on the association between dyslipidemia and hypertension. Zhonghua Liu Xing Bing Xue Za Zhi 2009; 30:554-558.
4. Harada K, Kariya T, Tanaka A, Toba A, Imai Y, Aoyama R, et al. HDL-cholesterol determines nocturnal blood pressure decline in the elderly with treated hypertension. Circulation 2011; 124:A15401.
5. Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, et al. High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation 1989; 79:8–15.
6. Hottenga JJ, Boomsma DI, Kupper N, Posthuma D, Snieder H, Willemsen G, et al. Heritability and stability of resting blood pressure. Twin Res Hum Genet 2005; 8:499–508
7. Tsai YS, Kim HJ, Takahashi N, Kim HS, Hagaman JR, Kim JK, et al. Hypertension and abnormal fat distribution but not insulin resistance in mice with P465L PPAR gamma. J Clin Invest 2004; 114:240–249.
8. Gouni-Berthold I, Giannakidou E, Muller-Wieland D, Faust M, Kotzka J, Berthold HK, et al. Peroxisorne proliferator-activated receptor gamma 2 Pro12Ala and endothelial nitric oxide synthase-4a/b gene polymorphisms are not associated with hypertension in diabetes mellitus type 2. J Hypertens 2005; 23: 301–308.
9. Ostgren CJ, Lindblad U, Melander O, Melander A, Groop L, Rastam L. Peroxisome proliferator activated receptor-gamma Pro12Ala polymorphism and the association with blood pressure in type 2 diabetes: Skaraborg Hypertension and Diabetes Project. J Hypertens 2003; 21: 1657–1662.
10. Stefanski A, Majkowska L, Ciechanowicz A, Frankow M, Safranow K, Parczewski M, et al. Association between the Pro12Ala variant of the peroxisome proliferator- activated receptor gamma 2 gene and increased 24-h diastolic blood pressure in obese patients with type II diabetes. J Hum Hypertens 2006; 20:684–692.
11. World Health Organization. International Society of Hypertension guidelines for the management of hypertension. GuidelinesSubcommittee. J Hypertens 1999; 17:151–183.
12. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285:2486–2497.
13. Hardy GH. Mendelian proportions in a mixed population. Science 1908;18:49–5014.
14. Weinberg W. On the demonstration of heredity in man. In: Boyer SH. editor. Papers on human genetics.1963. Prentice-Hall. Englewood Cliffs NJ; 1908.
15. Yen CJ, Beamer BA, Negri C, Silver K, Brown KA, Yarnall DP, et al. Molecular scanning of the human peroxisome proliferator-activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun 1997; 241: 270–274.
16. Lu Z, Dong B, Mo X, Chen T, Wu H, Zhang Y, et al. Pro12Ala polymorphism in PPAR c 2 associated with essential hypertension in Chinese nonagenarians/-centenarians. Exp Gerontol 2008; 43:1108–1113.
17. Gu SJ, Guo ZR, Wu M, Ding Y, Luo WS. Association of peroxisome proliferator-activated receptor g polymorphisms and haplotypes with essential hypertension. Genet Test Mol Biomarkers 2013; 17:1-6.
18. Wang Y, Liu C. Quantitative evaluation of common polymorphism (rs1801282) in the PPARg2 gene and hypertension susceptibility. Gene 2012; 502:159–162.
19. Oda E, Kawai R. High-density lipoprotein cholesterol is positively associated with hypertension in apparently healthy Japanese men and women. Br J Biomed Sci 2011; 68:29-33.
20. Sugawara A, Uruno A, Kudo M, Matsuda K, Yang CW, Ito S. Effects of PPAR-γ on hypertension, atherosclerosis, and chronic kidney disease. Endocr J 2010; 57:847-852.
21. Benkirane K, Viel EC, Amiri F, Schiffrin EL. Peroxisome proliferator-activated receptor gamma regulates angiotensin II-stimulated phosphatidyl-inositol 3-kinase and mitogen-activated protein kinase in blood vessels in vivo. Hypertension 2006; 47:102-108. 
22. Ji Y, Liu J, Wang Z, Liu N, Gou W. PPAR gamma agonist, rosiglitazone, regulates angiotensin II-induced vascular inflammation through the TLR4-dependent signaling pathway. Lab Invest 2009; 89: 887-902.
23. 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.