Skip to main content
SpringerLink
Log in

Association between angiotensin converting enzyme gene insertion/deletion polymorphism and intracerebral haemorrhage in North Indian population: a case control study and meta-analysis

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

The purpose of this study was to determine the relationship between Angiotensin converting enzyme (ACE) insertion/deletion polymorphism and ICH with an ACE level in a North Indian population. Patient with ICH and age- and sex- matched control subjects were recruited. Case control study design was used. Genotyping was performed by using Polymerase chain reaction. Serum ACE levels were measured by colorimetric method. Our results were integrated with other reported studies across different countries in a meta-analysis. One hundred and six patients with ICH and 106 age- and sex- matched control subjects were recruited. Mean age of cases and control subjects were 53.4 ± 1 and 52.9 ± 13.4, respectively. The DD genotypes were more frequency distributed in cases compared with controls (OR 2; 95 % CI, 1.02–3.8, P = 0.04) under a recessive model of inheritance. Meta-analysis suggests significant association between ACE I/D polymorphism and risk of ICH (OR 1.98; 95 % CI, 1.53–2.57) under the recessive model of inheritance and under the dominant model of inheritance (OR 1.31; 95 % CI, 1.18–1.45). The findings of the present study show a significant association between ACE insertion/deletion polymorphism and ICH. Meta-analysis indicate that ACE I/D polymorphism may be a susceptible marker for risk factor of ICH in Asian population.

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. Strong K, Mathers C, Bonita R (2007) Preventing stroke: saving lives around the world. Lancet Neurol 6(2):182–187

    Article  PubMed  Google Scholar 

  2. Feigin VL, Lawes CMM, Bennett DA, Barker-Collo SL, Parag V (2009) Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol 8(4):355–369

    Article  PubMed  Google Scholar 

  3. Soubrier F, Alhenc-Gelas F, Hubert C, Allegrini J, John M, Tregear G et al (1988) Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning. Proc Natl Acad Sci USA 85(24):9386–9390

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Rigat B, Hubert C, Corvol P, Soubrier F (1992) PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res 20(6):1433

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier 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(4):1343–1346

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Agerholm-Larsen B, Nordestgaard BG, Tybjaerg-Hansen A (2000) ACE gene polymorphism in cardiovascular disease: meta-analyses of small and large studies in whites. Arterioscler Thromb Vasc Biol 20(2):484–492

    Article  CAS  PubMed  Google Scholar 

  7. Chen Y, Dong S, He M, Qi T, Zhu W (2013) Angiotensin-converting enzyme insertion/deletion polymorphism and risk of myocardial infarction in an updated meta-analysis based on 34993 participants. Gene 522(2):196–205

    Article  CAS  PubMed  Google Scholar 

  8. Ramachandran V, Ismail P, Stanslas J, Shamsudin N, Moin S, Jas RM (2008) Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects. J Renin Angiotensin Aldosterone Syst 9(4):208–214

    Article  CAS  PubMed  Google Scholar 

  9. Li X, Li Y, Jia N, Guo S, Chu S, Niu W (2012) Angiotensin-converting enzyme gene deletion allele increases the risk of left ventricular hypertrophy: evidence from a meta-analysis. Mol Biol Rep 39(12):10063–10075

    Article  CAS  PubMed  Google Scholar 

  10. Miners JS, Ashby E, Van Helmond Z, Chalmers KA, Palmer LE, Love S et al (2008) Angiotensin-converting enzyme (ACE) levels and activity in Alzheimer’s disease, and relationship of perivascular ACE-1 to cerebral amyloid angiopathy. Neuropathol Appl Neurobiol 34(2):181–193

    Article  CAS  PubMed  Google Scholar 

  11. Lee YH, Choi SJ, Ji JD, Song GG (2012) Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and susceptibility to vasculitis: a meta-analysis. J Renin Angiotensin Aldosterone Syst 13(1):196–201

    Article  CAS  PubMed  Google Scholar 

  12. Qin H, Zhang L, Xu G, Pan X (2013) Association of angiotensin-converting enzyme insertion/deletion polymorphism (rs4646994) with the risk of primary intracerebral hemorrhage. Neurol Res 35(6):545–552

    Article  CAS  PubMed  Google Scholar 

  13. Aho K, Harmsen P, Hatano S, Marquardsen J, Smirnov VE, Strasser T (1980) Cerebrovascular disease in the community: results of a WHO collaborative study. Bull World Health Organ 58(1):113–130

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Kumar A, Vivekanandhan S, Srivastava A, Tripathi M, Padma Srivastava MV, Saini N et al. (2014) Association between angiotensin converting enzyme gene insertion/deletion polymorphism and ischemic stroke in north Indian population: a case-control study and meta-analysis. Neurol Res [Epub ahead of print]

  15. Kumar A, Sagar R, Kumar P, Sahu JK, Grover A, Srivastava AK et al (2013) Identification of genetic contribution to ischemic stroke by screening of single nucleotide polymorphisms in stroke patients by using a case control study design (Study protocol). BMC Neurol 13(1):136

    Article  PubMed Central  PubMed  Google Scholar 

  16. Kalita J, Somarajan BI, Kumar B, Mittal B, Misra UK (2011) A study of ACE and ADD1 polymorphism in ischemic and hemorrhagic stroke. Clin Chim Acta 412(7–8):642–646

    Article  CAS  PubMed  Google Scholar 

  17. Chiang FT, Hsu KL, Chen WM, Tseng CD, Tseng YZ (1998) Determination of angiotensin-converting enzyme gene polymorphisms: stepdown PCR increases detection of heterozygotes. Clin Chem 44(6 Pt 1):1353–1356

    CAS  PubMed  Google Scholar 

  18. Nirmal S, Tripathi M, Shastri SS, Sagar R, S V (2011) Association of Angiotensin-converting enzyme insertion(I)/deletion (D) genotype in Alzheimer’s disease patients of north Indian population. Int J Neurosci 121(10):557–561

    Article  CAS  PubMed  Google Scholar 

  19. Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F et al (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(1):197–205

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Pitt B (1994) Angiotensin-converting enzyme inhibitors in patients with coronary atherosclerosis. Am Heart J 128(6 Pt 2):1328–1332

    Article  CAS  PubMed  Google Scholar 

  21. Villard E, Soubrier F (1996) Molecular biology and genetics of the angiotensin-I-converting enzyme: potential implications in cardiovascular diseases. Cardiovasc Res 32(6):999–1007

    Article  CAS  PubMed  Google Scholar 

  22. Moncada R, Pulmer R, Higgs E (1995) Generation of prostacyclin and endothelium derived relaxing factor from endothelial cell nitric oxide synthase gene. Proc Natl Acad Sci USA 92:1137–1141

    Article  Google Scholar 

  23. Nawaz SK, Hasnain S (2011) Effect of ACE polymorphisms on the association between noise and hypertension in a Pakistani population. J Renin Angiotensin Aldosterone Syst 12(4):516–520

    Article  CAS  PubMed  Google Scholar 

  24. Jeng JR, Harn HJ, Jeng CY, Yueh KC, Shieh SM (1997) Angiotensin I converting enzyme gene polymorphism in Chinese patients with hypertension. Am J Hypertens 10(5 Pt 1):558–561

    Article  CAS  PubMed  Google Scholar 

  25. Zhu M, Zhang J, Nie S, Yan W (2012) Associations of ACE I/D, AGT M235T gene polymorphisms with pregnancy induced hypertension in Chinese population: a meta-analysis. J Assist Reprod Genet 29(9):921–932

    Article  PubMed Central  PubMed  Google Scholar 

  26. Dardiotis E, Jagiella J, Xiromerisiou G, Dardioti M, Vogiatzi C, Urbanik A et al (2011) Angiotensin-converting enzyme tag single nucleotide polymorphisms in patients with intracerebral hemorrhage. Pharmacogenet Genomics 21(3):136–141

    Article  CAS  PubMed  Google Scholar 

  27. Higashimori K, Zhao Y, Higaki J, Kamitani A, Katsuya T, Nakura J et al (1993) Association analysis of a polymorphism of the angiotensin converting enzyme gene with essential hypertension in the Japanese population. Biochem Biophys Res Commun 191(2):399–404

    Article  CAS  PubMed  Google Scholar 

  28. Vassilikioti S, Doumas M, Douma S, Petidis K, Karagiannis A, Balaska K et al (1996) Angiotensin converting enzyme gene polymorphism is not related to essential hypertension in a Greek population. Am J Hypertens 9(7):700–702

    Article  CAS  PubMed  Google Scholar 

  29. Chiang FT, Lai ZP, Chern TH, Tseng CD, Hsu KL, Lo HM et al (1997) Lack of association of the angiotensin converting enzyme polymorphism with essential hypertension in a Chinese population. Am J Hypertens 10(2):197–201

    Article  CAS  PubMed  Google Scholar 

  30. Samarasekera N, Smith C, Al-Shahi SR (2012) The association between cerebral amyloid angiopathy and intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatr 83(3):275–281

    Article  PubMed  Google Scholar 

  31. Cohen BA, Biller J (1992) Hemorrhagic stroke due to cerebral vasculitis and the role of immunosuppressive therapy. Neurosurg Clin N Am 3(3):611–624

    CAS  PubMed  Google Scholar 

  32. Song GG, Kim J-H, Lee YH (2013) Associations between the insertion/deletion polymorphism of the angiotensin-converting enzyme and susceptibility to aortic aneurysms: a meta-analysis. J Renin Angiotensin Aldosterone Syst [Epub ahead of print]

  33. Misra UK, Kalita J, Somarajan BI, Kumar B, Das M, Mittal B (2012) Do ACE (rs4646994) and αADDUCIN (rs4961) gene polymorphisms predict the recurrence of hypertensive intracerebral hemorrhage? Neurol Sci 33(5):1071–1077

    Article  PubMed  Google Scholar 

  34. Kalita J, Misra UK, Bindu IS, Kumar B, Mittal B (2011) Angiotensin-converting enzyme (rs4646994) and α ADDUCIN (rs4961) gene polymorphisms’ study in primary spontaneous intracerebral hemorrhage. Neurol India 59(1):41–46

    Article  CAS  PubMed  Google Scholar 

  35. Huang Y, Li G, Lan H, Zhao G, Huang C (2014) Angiotensin-converting enzyme insertion/deletion gene polymorphisms and risk of intracerebral hemorrhage: a meta-analysis of epidemiologic studies. J Renin Angiotensin Aldosterone Syst 15(1):32–38

  36. Slowik A, Turaj W, Dziedzic T, Haefele A, Pera J, Malecki MT et al (2004) DD genotype of ACE gene is a risk factor for intracerebral hemorrhage. Neurology 63(2):359–361

    Article  CAS  PubMed  Google Scholar 

  37. Sun Y, Liu Y, Watts LT, Sun Q, Zhong Z, Yang G-Y et al (2013) Genetic associations of angiotensin-converting enzyme with primary intracerebral hemorrhage: a meta-analysis. PLoS One 8(6):e67402

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was financially supported by Indian Council of Medical Research, Government of India.

Conflict of interest

There is no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neurology, Neurosciences Center, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

    A. Kumar, K. Prasad, M. V. P. Srivastava & M. Tripathi

  2. Department of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi, India

    S. Vivekanandhan

  3. R P Center, All India Institute of Medical Sciences, New Delhi, India

    A. Srivastava & S. Goswami

Authors
  1. A. Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Prasad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Vivekanandhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Srivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Goswami
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. V. P. Srivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Tripathi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Kumar.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, A., Prasad, K., Vivekanandhan, S. et al. Association between angiotensin converting enzyme gene insertion/deletion polymorphism and intracerebral haemorrhage in North Indian population: a case control study and meta-analysis. Neurol Sci 35, 1983–1990 (2014). https://doi.org/10.1007/s10072-014-1877-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-014-1877-3

Keywords

Search

Navigation