Angiotensin-Converting Enzyme Gene 2350 G/A Polymorphism Is Associated with Left Ventricular Hypertrophy but Not Essential Hypertension

Abstract

The angiotensin-converting enzyme (ACE) gene (ACE) is one of the most studied candidate genes related to essential hypertension (EH) and left ventricular hypertrophy (LVH). ACE rs4343 synonymous coding polymorphism (2350 G/A) is known among the polymorphisms of this gene to have the most significant effect on plasma ACE concentrations. The aim of the present study was to investigate the association of this polymorphism with EH and LVH in 440 subjects (246 EH patients and 194 controls) from a Chinese Han population. In this study, 2350 G/A genotypes were identified by polymerase chain reaction and restriction digestion in all study participants, and left ventricular mass was assessed by 2-mode echocardiography in 178 untreated EH patients. There was no significant difference in either genotype distribution (p=0.3659) or allele frequency (p=0.1453) between EH and control groups. In addition, the 2350 G/A polymorphism had no effect on blood pressure in either controls or untreated EH patients. The distribution of genotypes differed significantly when patients with LVH were examined, i.e., 14.71% GG, 54.41% GA, and 30.88% AA patients had this complication, and 36.36% GG, 42.73% GA, and 20.91% AA patients did not (p=0.0070). The LVH patients had a higher A allele frequency (58.09%) than patients without LVH (42.27%) (p=0.0037). Logistic regression analysis revealed that the association between the A allele and LVH was independent of age, blood pressure, and body mass index. The relative risk of LVH in patients bearing the A allele (GA+AA group) compared with that of GG hypertensive patients was 3.31 (95% confidence interval [CI]: 1.43 to 7.68). These findings suggest an association between LVH and the 2350A allele in hypertensive patients.

References

  1. 1

    Ward R : Familial aggregation and genetic epidemiology of blood pressure, in Laragh JH, Brenner BM ( eds): Hypertension: Pathophysiology, Diagnosis, and Management. New York, Raven Press, 1990, pp 81–100.

    Google Scholar 

  2. 2

    Takai S, Jin D, Sakaguchi M, Miyazaki M : Significant target organs for hypertension and cardiac hypertrophy by angiotensin-converting enzyme inhibitors. Hypertens Res 2004; 27: 213–219.

    CAS  Article  Google Scholar 

  3. 3

    Watt GC, Harrap SB, Foy CJ, et al: Abnormalities of glucocorticoid metabolism and the renin-angiotensin system: a four-corners approach to the identification of genetic determinants of blood pressure. J Hypertens 1992; 10: 473–482.

    CAS  PubMed  Article  Google Scholar 

  4. 4

    Kawamoto R, Kohara K, Tabara Y, Miki T : An interaction between systolic blood pressure and angiotensin-converting enzyme gene polymorphism on carotid atherosclerosis. Hypertens Res 2002; 25: 875–880.

    CAS  PubMed  Article  Google Scholar 

  5. 5

    Danser AHJ, Schalekamp MADH, Bax WA, et al: Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation 1995; 92: 1387–1388.

    CAS  PubMed  Article  Google Scholar 

  6. 6

    Zee R, Lou YK, Griffiths LR, et al: Association of a polymorphism of angiotensin converting enzyme gene with essential hypertension. Biochem Biophys Res Commun 1992; 184: 9–15.

    CAS  PubMed  Article  Google Scholar 

  7. 7

    Tamaki S, Nakamura Y, Tsujita Y, et al: Polymorphism of the angiotensin converting enzyme gene and blood pressure in a Japanese general population (the Shigaraki Study). Hypertens Res 2002; 25: 843–848.

    CAS  PubMed  Article  Google Scholar 

  8. 8

    Tanaka C, Kamide K, Takiuchi S, et al: An alternative fast and convenient genotyping method for the screening of angiotensin converting enzyme gene polymorphisms. Hypertens Res 2003; 26: 301–306.

    CAS  PubMed  Article  Google Scholar 

  9. 9

    Levy D, DeStefano AL, Larson MG, et al: Evidence for a gene influencing blood pressure on chromosome 17: genome scan linkage results for longitudinal blood pressure phenotypes in subjects from the Framingham Heart Study. Hypertension 2000; 36: 477–483.

    CAS  PubMed  Article  Google Scholar 

  10. 10

    Zhu X, Bouzekri N, Southam L, et al: Linkage and association analysis of angiotensin I–converting enzyme (ACE)−gene polymorphisms with ACE concentration and blood pressure. Am J Hum Genet 2001; 68: 1139–1148.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  11. 11

    Sahn DJ, De Maria A, Kisslo J, Weyman A : The Committee on M-Mode Standardization of the American Society: recommendations regarding quantitation in M-mode echocardiography. Circulation 1978; 58: 1071–1083.

    Google Scholar 

  12. 12

    Devereux RB, Reichek N : Echocardiographic determination of left ventricular mass in man: anatomic validation of the method. Circulation 1977; 55: 613–618.

    CAS  PubMed  Article  Google Scholar 

  13. 13

    Levy D : Clinical significance of left ventricular hypertrophy: insights from the Framingham Study. J Cardiovasc Pharmacol 1991; 17: 1–6.

    Article  Google Scholar 

  14. 14

    Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH : Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med 1991; 114: 345–352.

    CAS  PubMed  Article  Google Scholar 

  15. 15

    Miller SA, Dykes DD, Polesky HF : A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16

    Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F : An insertion/deletion polymorphism in the angiotensin I–converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990; 86: 1343–1346.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17

    O'Donnell CJ, Lindpaitner K, Larson MG, et al: Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation 1998; 97: 1766–1772.

    CAS  PubMed  Article  Google Scholar 

  18. 18

    Fornage M, Amos CI, Kardia S, et al: Variation in the region of the angiotensin-converting enzyme gene influences interindividual differences in blood pressure levels in young white males. Circulation 1998; 97: 1773–1779.

    CAS  PubMed  Article  Google Scholar 

  19. 19

    Higaki J, Baba S, Katsuya T, et al: Deletion allele of angiotensin-converting enzyme gene increases risk of essential hypertension in Japanese men. Circulation 2000; 101: 2060.

    CAS  PubMed  Article  Google Scholar 

  20. 20

    Gesang L, Liu G, Cen W, et al: Angiotensin-converting enzyme gene polymorphism and its association with essential hypertension in a Tibetan population. Hypertens Res 2002; 25: 481–485.

    CAS  PubMed  Article  Google Scholar 

  21. 21

    Staessen JA, Wang JG, Ginocchio G, et al: The deletion/insertion polymorphism of the angiotensin converting enzyme gene and cardiovascular renal risk. J Hypertens 1997; 15: 1579–1592.

    CAS  PubMed  Article  Google Scholar 

  22. 22

    Czarnecka D, Kawecka-Jaszcz K, Stolarz K, et al: Genetic factors in hypertension. Angiotensin-converting enzyme polymorphism. Kardiol Pol 2004; 61: 1–10.

    PubMed  Google Scholar 

  23. 23

    Saeed Mahmood M, Saboohi K, Osman Ali S, Bokhari AM, Frossard PM : Association of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with essential hypertension. J Hum Hypertens 2003; 17: 719–723.

    CAS  PubMed  Article  Google Scholar 

  24. 24

    Asai T, Kushiro T, Fujita H, Kanmatsuse K : Different effects on inhibition of cardiac hypertrophy in spontaneously hypertensive rats by monotherapy and combination therapy of adrenergic receptor antagonists and/or the angiotensin II type 1 receptor blocker under comparable blood pressure reduction. Hypertens Res 2005; 28: 79–87.

    CAS  PubMed  Article  Google Scholar 

  25. 25

    Yasumoto K, Takata M, Ueno H, Tomoda F, Inoue H : Relation of circulating blood volume to left ventricular geometry in essential hypertension. Hypertens Res 2002; 25: 703–710.

    PubMed  Article  Google Scholar 

  26. 26

    Fu Y, Katsuya T, Matsuo A, et al: Relationship of bradykinin B2 receptor gene polymorphism with essential hypertension and left ventricular hypertrophy. Hypertens Res 2004; 27: 933–938.

    CAS  PubMed  Article  Google Scholar 

  27. 27

    Iwashima Y, Horio T, Kuroda S, Takishita S, Kawano Y : Influence of plasma aldosterone on left ventricular geometry and diastolic function in treated essential hypertension. Hypertens Res 2002; 25: 49–56.

    CAS  Article  Google Scholar 

  28. 28

    Schunkert H, Hense H, Holmer S, et al: Association between a deletion polymorphism of the angiotensin converting enzyme gene and left ventricular hypertrophy. N Engl J Med 1994; 330: 1634–1638.

    CAS  PubMed  Article  Google Scholar 

  29. 29

    Inomata H, Watanabe T, Iizuka Y, et al: Identification of quantitative trait loci for cardiac hypertrophy in two different strains of the spontaneously hypertensive rat. Hypertens Res 2005; 28: 273–281.

    CAS  PubMed  Article  Google Scholar 

  30. 30

    Saeed M, Saleheen D, Siddiqui S, Khan A, Butt ZA, Frossard PM : Association of angiotensin converting enzyme gene polymorphisms with left ventricular hypertrophy. Hypertens Res 2005; 28: 345–349.

    CAS  PubMed  Article  Google Scholar 

  31. 31

    Saeed M, Mekan SF, Rabbani MA, Arain FM, Arif M, Shaharyar S : Angiotensin converting enzyme (ACE) gene polymorphisms and lupus disease severity: a promising link. Ann Rheum Dis 2005; 64; 164–165.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. 32

    Kehoe PG, Katzov H, Feuk L, et al: Haplotypes extending across ACE are associated with Alzheimer's disease. Hum Mol Genet 2003; 12: 8859–8867.

    Article  Google Scholar 

  33. 33

    Duan J, Wainwright MS, Comeron JM, et al: Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum Mol Genet 2003; 12: 205–216.

    CAS  PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jian-Hua Zhu.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Pan, M., Zhu, JH., Liu, ZH. et al. Angiotensin-Converting Enzyme Gene 2350 G/A Polymorphism Is Associated with Left Ventricular Hypertrophy but Not Essential Hypertension. Hypertens Res 30, 31–37 (2007). https://doi.org/10.1291/hypres.30.31

Download citation

Keywords

  • angiotensin-converting enzyme
  • genetic polymorphism
  • essential hypertension
  • left ventricular hypertrophy

Further reading

Search