Association of polymorphisms in angiotensin II receptor genes with aldosterone-producing adenoma

  • Jinzhi Ouyang (欧阳金芝)
  • Zhun Wu (吴 准)
  • Jinchun Xing (邢金春)
  • Yongji Yan (闫永吉)
  • Guoxi Zhang (张国玺)
  • Baojun Wang (王保军)
  • Hongzhao Li (李宏召)
  • Xin Ma (马 鑫)
  • Xu Zhang (张 旭)Email author


This study examined the association of polymorphisms in angiotensin II receptor genes (AT 1 R and AT 2 R) with the risk for aldosterone-producing adenoma (APA) in a Chinese Han population. Four polymorphisms including rs5182 (573T/C) in exon 4, rs5186 (1166A/C) in 3′-untranslated region (3′-UTR) in AT 1 R gene and rs5194 (2274G/A) in 3′-UTR, rs1403543 (1675G/A) in intron 1 in AT 2 R gene were detected in 148 APA patients and 192 normal subjects (serving as control) by using a MGB-Taqman probe. The distribution of genotypes of each locus was in accordance with Hardy-Weinberg Equilibrium (HWE) in the APA and control groups (P>0.05). The allele A frequency at rs5194 was significantly higher in the APA group (0.49) than in the control group (0.35) (χ 2=12.08, P=0.001). Subjects with homozygotic genotype AA and heterozygotic genotype GA were at an increased risk for APA as compared to those with GG genotype (OR=2.66, 95% CI=1.45–4.87; OR=1.67, 95% CI=1.02–2.74). Furthermore, rs5194 single-nucleotide polymorphism (SNP) at AT 2 R gene was significantly associated with APA in additive (OR=1.64, 95% CI=1.21–2.20, P=0.001), dominant (OR=1.94, 95% CI=1.23–3.06, P=0.003), and recessive model (OR=2.01, 95% CI=1.17–3.45, P=0.01). It was concluded that rs5194 polymorphism at AT 2 R gene was associated with the risk for APA, which may constitute a genetic marker of APA.

Key words

aldosterone-producing adenoma angiotensinIIreceptor polymorphism 


  1. 1.
    Fallo F, Pistorello M, Pedini F, et al. In vitro evidence for local generation of renin and angiotensin II/III immunoreactivity by the human adrenal gland. Acta Endocrinol (Copenh), 1991,125(3):319–330Google Scholar
  2. 2.
    Gard PR. The role of angiotensin II in cognition and behavior. Eur J Pharmacol, 2002,438(1–2):1–14PubMedCrossRefGoogle Scholar
  3. 3.
    Thomas WG, Mendelsohn FA. Angiotensin receptors: form and function and distribution. Int J Biochem Cell Biol, 2003,35(6):774–779PubMedCrossRefGoogle Scholar
  4. 4.
    Alfakih K, Maqbool A, Sivananthan M, et al. Left ventricle mass index and the common, functional, X-linked angiotensin II type-2 receptor gene polymorphism (−1332 G/A) in patients with systemic hypertension. Hypertension, 2004,43(6):1189–1194PubMedCrossRefGoogle Scholar
  5. 5.
    Schmieder RE, Erdmann J, Delles C, et al. Effect of the angiotensin II type 2-receptor gene (+1675 G/A) on left ventricular structure in humans. J Am Coll Cardiol, 2001,37(1):175–182PubMedCrossRefGoogle Scholar
  6. 6.
    Koh WP, Yuan JM, Van Den Berg D, et al. Polymorphisms in angiotensin II type 1 receptor and angiotensin I-converting enzyme genes and breast cancer risk among Chinese women in Singapore. Carcinogenesis, 2005,26(2):459–464PubMedCrossRefGoogle Scholar
  7. 7.
    de Gasparo M, Catt KJ, Inagami T, et al. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev, 2000,52(3):415–472PubMedGoogle Scholar
  8. 8.
    Martin MM, Elton TS. The sequence and genomic organization of the human type 2 angiotensin II receptor. Biochem Biophys Res Commun, 1995,209(2):554–562PubMedCrossRefGoogle Scholar
  9. 9.
    Vinson GP, Ho MM, Puddefoot JR. The distribution of angiotensin II type 1 receptors, and the tissue renin-angiotensin systems. Mol Med Today, 1995,1(1): 35–39PubMedCrossRefGoogle Scholar
  10. 10.
    Aguilera G. Factors controlling steroid biosynthesis in the zona glomerulosa of the adrenal. J Steroid Biochem Mol Biol, 1993,45(1–3):147–151PubMedCrossRefGoogle Scholar
  11. 11.
    Hilbers U, Peters J, Bornstein SR, et al. Local renin-angiotensin system is involved in K+-induced aldosterone secretion from human adrenocortical NCI-H295 cells. Hypertension, 1999,33(4):1025–1030PubMedGoogle Scholar
  12. 12.
    Belloni AS, Andreis PG, Macchi V, et al. Distribution and functional significance of angiotensin-II AT1- and AT2-receptor subtypes in the rat adrenal gland. Endocr Res, 1998,24(1):1–15PubMedCrossRefGoogle Scholar
  13. 13.
    Nakajima M, Hutchinson HG, Fujinaga M, et al. The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer. Proc Natl Acad Sci U S A, 1995,92(23):10 663–10 667CrossRefGoogle Scholar
  14. 14.
    Inagami T, Eguchi S, Numaguchi K, et al. Cross-talk between angiotensin II receptors and the tyrosine kinases and phosphatases. J Am Soc Nephrol, 1999,10(Suppl): 11S57–11S61Google Scholar
  15. 15.
    Widdop RE, Jones ES, Hannan RE, et al. Angiotensin AT2 receptors: cardiovascular hope or hype? Br J Pharmacol, 2003,140(5):809–824PubMedCrossRefGoogle Scholar
  16. 16.
    Xu J, Carretero OA, Liu YH, et al. Role of AT2 receptors in the cardioprotective effect of AT1 antagonists in mice. Hypertension, 2002,40(3):244–250PubMedCrossRefGoogle Scholar
  17. 17.
    Wu L, Iwai M, Nakagami H, et al. Effect of angiotensin II type 1 receptor blockade on cardiac remodeling in angiotensin II type 2 receptor null mice. Arterioscler Thromb Vasc Biol, 2002,22(1):49–54PubMedCrossRefGoogle Scholar
  18. 18.
    Bonnardeaux A, Davies E, Jeunemaitre X, et al. Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension, 1994,24(1): 63–69PubMedGoogle Scholar
  19. 19.
    Kainulainen K, Perola M, Terwilliger J, et al. Evidence for involvement of the type 1 angiotensin II receptor locus in essential hypertension. Hypertension, 1999,33(3): 844–849PubMedGoogle Scholar
  20. 20.
    Diez J, Laviades C, Orbe J, et al. The A1166C polymorphism of the AT1 receptor gene is associated with collagen type I synthesis and myocardial stiffness in hypertensives. J Hypertens, 2003,21(11):2085–2092PubMedCrossRefGoogle Scholar
  21. 21.
    Zhang M, Ma H, Wang BS, et al. Angiotensin II type 2 receptor gene polymorphisms and cardioprotective role in essential hypertension. Heart Vessels, 2006,21(2):95–101PubMedCrossRefGoogle Scholar
  22. 22.
    Wu Z, Ni D, Yan Y, et al. Expression of angiotensin IIreceptors in aldosterone-producing adenoma of the adrenal gland and their clinical significance. J Huazhong Univ Sci Technolog Med Sci, 2010,30(4):486–489PubMedCrossRefGoogle Scholar
  23. 23.
    Jin XQ, Fukuda N, Su JZ, et al. Angiotensin II type 2 receptor gene transfer downregulates angiotensin II type 1a receptor in vascular smooth muscle cells. Hypertension, 2002,39(5):1021–1027PubMedCrossRefGoogle Scholar
  24. 24.
    Kuznetsova T, Staessen JA, Thijs L, et al. Left ventricular mass in relation to genetic variation in angiotensin II receptors, renin system genes, and sodium excretion. Circulation, 2004,110(17):2644–2650PubMedCrossRefGoogle Scholar
  25. 25.
    Herrmann SM, Nicaud V, Schmidt-Petersen K, et al. Angiotensin II type 2 receptor gene polymorphism and cardiovascular phenotypes: the GLAECO and GLAOLD studies. Eur J Heart Fail, 2002,4(6):707–712PubMedCrossRefGoogle Scholar
  26. 26.
    Yamada T, Horiuchi M, Dzau VJ. Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci USA, 1996,93(1):156–160PubMedCrossRefGoogle Scholar
  27. 27.
    Stoll M, Unger T. Angiotensin and its AT2 receptor: new insights into an old system. Regul Pept, 2001,99(2–3): 175–182PubMedCrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Jinzhi Ouyang (欧阳金芝)
    • 1
  • Zhun Wu (吴 准)
    • 3
  • Jinchun Xing (邢金春)
    • 3
  • Yongji Yan (闫永吉)
    • 4
  • Guoxi Zhang (张国玺)
    • 5
  • Baojun Wang (王保军)
    • 2
  • Hongzhao Li (李宏召)
    • 2
  • Xin Ma (马 鑫)
    • 2
  • Xu Zhang (张 旭)
    • 2
    Email author
  1. 1.Department of EndocrinologyChinese PLA General HospitalBeijingChina
  2. 2.Department of UrologyChinese PLA General HospitalBeijingChina
  3. 3.Department of Urologythe First Affiliated Hospital of Xiamen UniversityXiamenChina
  4. 4.Department of Urologythe Second Affiliated Hospital of Kunming Medical UniversityKunmingChina
  5. 5.Department of Urologythe First Affiliated Hospital of Gannan Medical UniversityGanzhouChina

Personalised recommendations