Skip to main content
SpringerLink
Log in

Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The angiotensin converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. Factor VII (FACTOR VII) is the first enzyme in the extrinsic pathway of the blood coagulation system and plays a key role in hemostasis; it also contributes to the occurrence of thrombotic events. In this study, we have examined the association of ACE and FACTOR VII gene in coronary heart disease patients (n = 300) and their age-matched controls (n = 300). Genotyping was done by PCR-RFLP method. No significant difference was observed in the distribution of I/D genotypes of ACE between cases and controls. In case of FACTOR VII R353Q polymorphism, there was not much difference in the distribution of alleles. AA genotype had protective effect for CHD (OR 0.56, 95% CI 0.37–0.83, P = 0.001). In case of FACTOR VII VNTR, there was difference in the distribution of alleles, H6 (73.5) and H7 (25.5) in cases, and H6 (70.5) and H7 (30.5) in controls. H6H7 and H7H7 genotypes had a protective effect for CHD with OR 0.27, 95% CI 0.18–0.41, P < 0.001, and OR 0.18, 95% CI 0.09–0.36, P < 0.001. Our study showed D allele of ACE to be associated with marginal risk of CHD, AA genotype of FACTOR VII R353Q and H6H7 and H7H7 genotypes of FACTOR VII VNTR showed protective effect for CHD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Magrini F, Reggiani P, Roberts N, Meazza R, Ciulla M, Zanchetti A (1988) Effects of angiotensin and angiotensin blockade on coronary circulation and coronary reserve. Am J Med 84:55–60

    Article  CAS  PubMed  Google Scholar 

  2. Mochizuki T, Eberli FR, Apstein CS, Lorell BH (1992) Exacerbation of ischemic dysfunction by angiotensin II in red cell-perfused rabbit hearts: effects on coronary flow, contractility, and high-energy phosphate metabolism. J Clin Invest 89:490–498

    Article  CAS  PubMed  Google Scholar 

  3. Robert Y, Zee L, Fernandez-Ortiz A, Macaya C, Pintor E, Lindpaintner K, Fernandez A (2001) ACE D/I polymorphism and incidence of post-PTCA restenosis: a prospective angiography-based evaluation. Hypertension 37:851–855

    Google Scholar 

  4. Ellis SG, Vandormael MG, Cowley MJ, DiSciascio G, Deligonul U, Topol EJ, Bulle TM (1990) Coronary morphological and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease: implication patient selection. Circulation 82:1193–1202

    CAS  PubMed  Google Scholar 

  5. Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, Buring J, Hennekens CH (1993) A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 332:706–711

    Article  Google Scholar 

  6. Iniguez A, Macaya C, Alfonso F, Goicolea J, Hernandez R, Zarco P (1994) Early angiographic changes of side branches arising from a Palmaz-Schatz stented coronary segment: results and clinical implications. J Am Coll Cardiol 23:911–915

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Tiret L, Rigat B, Visvikis S (1992) Evidence from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 51:197–205

    CAS  PubMed  Google Scholar 

  9. Villard E, Tiret L, Visvikis S (1996) Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by 2-QTL segregation-linkage analysis. Am J Hum Genet 58:1268–1278

    CAS  PubMed  Google Scholar 

  10. Ruiz J, Blanche H, Cohen N (1994) Insertion/deletion polymorphism of the angiotensin converting enzyme gene is strongly associated with coronary heart disease in non insulin dependent diabetes mellitus. Proc Natl Acad Sci USA 91:3662–3665

    Article  CAS  PubMed  Google Scholar 

  11. Lindpaintner K, Pfeffer MA, Kreutz R (1995) A prospective evaluation of an angiotensin converting enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 332:706–711

    Article  CAS  PubMed  Google Scholar 

  12. Hamon M, Fradin S, Denizet A, Filippi-Codaccioni E, Grollier G, Morello R (2003) Prospective evaluation of the effect of an angiotensin I converting enzyme gene polymorphism on the long term risk of major adverse cardiac events after percutaneous coronary intervention. Heart 89:321–325

    Article  CAS  PubMed  Google Scholar 

  13. Keavney B, McKenzie C, Parish S, Palmer A, Clark S, Youngman L (2000) Large scale test of hypothesized associations between the angiotensin converting enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls. Lancet 355:434–442

    CAS  PubMed  Google Scholar 

  14. Francois B, Bernard K (2002) Angiotensin converting enzyme insertion or deletion polymorphism and coronary restenosis: a meta-analysis of 16 studies. BMJ 325:517–520

    Article  Google Scholar 

  15. Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ (1993) Fibrinolytic activity of clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 2:1076–1079

    Article  Google Scholar 

  16. Rosendaal FR (2003) Clotting and myocardial infarction: a cycle of insights. J Thromb Haemost 1:640–642

    Article  CAS  PubMed  Google Scholar 

  17. Ghaddar HM, Folsom AR, Aleksic N, Hearne LB, Chambless LE, Morrissey JH, Wu KK (1998) Atherosclerosis risk in communities for the study investigators. Circulation 98:2815–2821

    CAS  PubMed  Google Scholar 

  18. Iacoviello L, Di Castelnuovo A, DeKnijff P, D’Orazio A, Amore C, Arboretti R, Kluft C, Donati MD (1998) Polymorphisms in the coagulation factor VII gene and the risk of myocardial infarction. N Engl J Med 338:78–85

    Article  Google Scholar 

  19. Cooper JA, Miller GJ, Bauer KA (2000) Comparison of novel hemostatic factors and conventional risk factors for prediction of coronary heart disease. Circulation 102:2816–2822

    CAS  PubMed  Google Scholar 

  20. Meade TW, Mellows S, Brozovic M (1986) Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 2:533–537

    Article  CAS  PubMed  Google Scholar 

  21. Junker R, Heinrich J, Schulte H, van de Loo J, Assmann G (1997) Coagulation factor VII and the risk of coronary heart disease in healthy men. Arterioscler Thromb Vasc Biol 17:1539–1544

    CAS  PubMed  Google Scholar 

  22. Sekar K, Qiong Y, Martin GL, Camargo AL, Tofler GH, Hirschhorn JN, Gabriel SB, O’Donnell CJ (2006) Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk. Thromb Vasc Biol 26:1405–1412

    Article  CAS  Google Scholar 

  23. Cortellaro M, Boschetti C, Cofrancesco E (1992) The PLAT Study: hemostatic function in relation to atherothrombotic ischemic events in vascular disease patients: principal results. Arterioscler Thromb 12:1063–1070

    CAS  PubMed  Google Scholar 

  24. Vaziri ND, Kennedy SC, Kennedy D, Gonzales E (1992) Coagulation, fibrinolytic, and inhibitory proteins in acute myocardial infarction and angina pectoris. Am J Med 93:651–657

    Article  CAS  PubMed  Google Scholar 

  25. Feng D, Tofler GF, Larson MG, O’Donnell CJ, Lipinska I, Schmitz C, Sutherland PA, Johnstone MT, Muller JE, D’Agostino RB, Levy D, Lindpaintner K (2000) Factor VII gene polymorphism, factor VII levels, and prevalent cardiovascular disease—The Framingham Heart Study. Arterioscler Thromb Vasc Biol 20:593–600

    CAS  PubMed  Google Scholar 

  26. Green F, Kelleher C, Wilkes H, Temple A, Meade T, Humphries S (1991) A common genetic polymorphism associated with lower coagulation factor VII levels in healthy individuals. Arterioscler Thromb 11:540–546

    CAS  PubMed  Google Scholar 

  27. Saha N, Liu Y, Heng CK, Hong S, Low PS, Tay JSH (1994) Association of factor VII genotype with plasma factor VII activity and antigen levels in healthy Indian adults and interaction with triglycerides. Arterioscler Thromb 14:1923–1927

    CAS  PubMed  Google Scholar 

  28. Bernardi F, Arcieri P, Bertina RM, Chiarotti F, Corral J, Pinotti M (1997) Contribution of factor VII genotype to activated FVII levels: differences in genotype frequencies between northern and southern European populations. Arterioscler Thromb Vasc Biol 17:2548–2553

    CAS  PubMed  Google Scholar 

  29. Masakazu O, Satoshi A, Sadatoshi B, Masahiko S, Takashi K, Shiro S, Tatsuru M, Hitoshi T, Hiroyuki T, Yoshihiko A, Yoshifumi T, Shigeki T, Shinichi M, Ikuro M, Chuwa T (2004) R353Q polymorphism, activated factor VII, and risk of premature myocardial infarction in Japanese men. Circ J 68:520–525

    Article  Google Scholar 

  30. Lane A, Green F, Scarabin PY (1996) Factor VII Arg/Gln 353 polymorphism determines factor VII coagulant activity in patients with myocardial infarction (MI) and control subjects in Belfast and in France but is not a strong indicator of MI risk in the ECTIM study. Atherosclerosis 119:119–127

    Article  CAS  PubMed  Google Scholar 

  31. Peyvandi F, Mannucci PM, Bucciarelli P, Zeinali S, Akhavan S, Sacchi E, Merlini PA, Perry DJ (2000) A novel polymorphism in intron 1a of the human factor VII gene (G73A): study of a healthy Italian population and of 190 young survivors of myocardial infarction. Br J Haematol 108(2):247–253

    Article  CAS  PubMed  Google Scholar 

  32. Marchetti G, Patracchini G, Gemmati D et al (1992) Detection of two missense mutations and characterization of a repeat polymorphism in factor VII gene. Hum Genet 89:497–502

    Article  CAS  PubMed  Google Scholar 

  33. Malley JP, Jean PB, Maslen CL, Roger Illingworth D (1998) Angiotensin-converting enzyme DD genotype and cardiovascular disease in heterozygous familial hypercholesterolemia. Circulation 97:1780–1783

    Google Scholar 

  34. Mata BT, Herran R (2004) ACE and p22 (phox) polymorphisms and the risk of CHD in a low risk Spanish population. Int J Cardiol 95:145–151

    Article  Google Scholar 

  35. Oei HH, Sayed TFA (2005) The association between ACE gene polymorphisms and coronary calcification—The Rotterdam Coronary Calcification Study. Atherosclerosis 182:169–173

    Article  CAS  PubMed  Google Scholar 

  36. Sayed TFA, Schut AF (2005) ACE gene polymorphism and cardiovascular morbidity and mortality. J Med Genet 42:26–30

    Article  CAS  Google Scholar 

  37. Ashavaid TF, Shalia KK, Kondkar AA, Todur SP, Nair KG, Nair SR (2002) Gene polymorphism and coronary risk factors in Indian population. Clin Chem Lab Med 40(10):975–985

    Article  CAS  PubMed  Google Scholar 

  38. Ribichini F, Steffenino G, Dellavalle A, Matullo G, Colajanni E, Camilla T, Vado A, Benetton G, Uslenghi E, Piazza A (1998) Plasma activity and insertion/deletion polymorphism of angiotensin I-converting enzyme: major risk factor and a marker of risk for coronary stent restenosis. Circulation 97:147–154

    CAS  PubMed  Google Scholar 

  39. Wang XL, Wang J, McCredie RM, Wilcken DEL (1997) Polymorphisms of factor V, factor VII, and fibrinogen genes: relevance to severity of coronary artery disease. Arterioscler Thromb Vasc Biol 17:246–251

    CAS  PubMed  Google Scholar 

  40. Pollak ES, Hung H-L, Godin W, Overton GC, High KA (1996) Functional characterization of the human factor VII 5′-flanking region. J Biol Chem 271:1738–1747

    Article  CAS  PubMed  Google Scholar 

  41. Van’t Hooft FM, Silveira A, Tornvall P (1999) Two common functional polymorphisms in the promoter region of the coagulation factor VII gene determining plasma factor VII activity and mass concentration. Blood 93:3432–3441

    Google Scholar 

  42. Humphries SE, Lane A, Green FR, Cooper J, Miller GJ (1994) Factor VII coagulant activity and antigen levels in healthy men are determined by interaction between factor VII genotype and plasma triglyceride concentration. Arterioscler Thromb 14:193–198

    CAS  PubMed  Google Scholar 

  43. Hembrough TA, Swartz GM, Papathanassiu A, Vlasuk GP, Rote WE, Green SJ, Pribluda VS (2003) Tissue factor/factor VIIa inhibitors block angiogenesis and tumor growth through a non hemostatic mechanism. Cancer Res 63:2997–3000

    CAS  PubMed  Google Scholar 

  44. De Jonge E, Friederich PW, Vlasuk GP, Rote WE, Vroom MB, Levi M, Vander PT (2003) Activation of coagulation by administration of recombinant factor VIIa elicits interleukin (IL) 6 and IL-8 release in healthy human subjects. Clin Diagn Lab Immunol 10:495–497

    PubMed  Google Scholar 

  45. Moser M, Patterson C (2003) Thrombin and vascular development: a sticky subject. Arterioscler Thromb Vasc Biol 23:922–930

    Article  CAS  PubMed  Google Scholar 

  46. Sicker T, Wuchold F, Kaiser B, Glusa E (2001) Systemic vascular effects of thrombin and thrombin receptor activating peptide in rats. Thromb Res 101:467–475

    Article  CAS  PubMed  Google Scholar 

  47. Major CD, Santulli RJ, Derian CK, Andrade-Gordon P (2003) Extracellular mediators in atherosclerosis and thrombosis: lessons from thrombin receptor knockout mice. Arterioscler Thromb Vasc Biol 23:931–939

    Article  CAS  PubMed  Google Scholar 

  48. Lariviere R, Lebel M (2003) Endothelin-1 in chronic renal failure and hypertension. Can J Physiol Pharmacol 81:607–621

    Article  CAS  PubMed  Google Scholar 

  49. Pinotti M, Toso R, Girelli D, Bindini D, Ferraresi P, Maria L, Corrocher P, Marchetti G, Bernardi F (2000) Modulation of factor VII levels by intron 7 polymorphisms: population and in vitro studies. Blood 95:3423–3428

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from Council of Scientific and Industrial Research, Ministry of Human Resource and Development, New Delhi, India. We thank Dr. Gurbir Singh and Dr. G.S. Kalra, Fortis Hospital, Mohali, India for their kind help and co-operation.

Author information

Authors and Affiliations

  1. Department of Biotechnology, Panjab University, Chandigarh, 160014, India

    R. C. Sobti, Nishi Maithil & Hitender Thakur

  2. Department of Cardiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Yashpaul Sharma & K. K. Talwar

Authors
  1. R. C. Sobti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nishi Maithil
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hitender Thakur
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yashpaul Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. K. Talwar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. C. Sobti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sobti, R.C., Maithil, N., Thakur, H. et al. Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population. Mol Cell Biochem 341, 87–98 (2010). https://doi.org/10.1007/s11010-010-0440-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-010-0440-7

Keywords

Search

Navigation