Neurological Sciences

, Volume 33, Issue 5, pp 1071–1077 | Cite as

Do ACE (rs4646994) and αADDUCIN (rs4961) gene polymorphisms predict the recurrence of hypertensive intracerebral hemorrhage?

  • Usha K. Misra
  • Jayantee Kalita
  • Bindu I. Somarajan
  • Bishwanath Kumar
  • Moromi Das
  • Balraj Mittal
Original Article

Abstract

This study was undertaken to evaluate the role of ACE and αADDUCIN polymorphisms in patients with recurrent and nonrecurrent hypertensive intracerebral hemorrhage (ICH). A total of 101 nonrecurrent and 33 recurrent hypertensive ICH patients underwent an ACE (rs4646994) and αADDUCIN (rs4961) gene polymorphism study. The risk factors, clinical findings, CT scan abnormalities and functional outcome of recurrent and nonrecurrent ICH were compared. ACE (rs4646994) and αADDUCIN (rs4961) gene polymorphisms were also compared in the two groups and with 198 controls. The patients with recurrent ICH were older compared to those with nonrecurrent ICH and the other stroke risk factors were found in the two groups. Ganglionic–ganglionic pattern of recurrence was the commonest (75.6%) and all had at least one ICH in the location of hypertensive ICH. ACE DD genotype (OR6.18, 95%CI 2.93–13.02) and D allele (OR 2.43, 95%CI 1.70–3.47) were associated with nonrecurrent ICH compared to controls. In patients with recurrent ICH, DD genotype (OR 7.46, 95%CI 2.8–19.4) and D allele (OR 3.16, 95%CI 1.83–5.46) of ACE, and GW (OR 3.49, 95%CI 1.47–8.28), WW (OR 2.9, 95%CI 1.40–4.30) genotypes and W allele (OR 7.46, 95%CI 2.80–19.40) of αADDUCIN were more frequent compared to controls. Recurrent ICH also had higher frequency of WW genotype (OR 9.43, 95%CI 1.49–59.50) and W allele (OR 2.19, 95%CI 1.11–4.03) compared to nonrecurrent ICH. The frequency of DD + WW (P = 0.008) and DD/WW + ID/GW (P = 0.0001) genotypes in the recurrent ICH was higher than in the nonrecurrent ICH and the controls. Variant genotype combinations of ACE and αADDUCIN render the hypertensive patient more vulnerable to recurrent ICH.

Keywords

Hypertension ICH Recurrent intracerebral hemorrhage Gene polymorphism ACE αADDUCIN North India 

Notes

Acknowledgments

We thank the Indian Council of Medical Research for funding support.

References

  1. 1.
    Douglas MA, Haerer AF (1982) Long-term prognosis of hypertensive intracerebral hemorrhage. Stroke 13:488–491PubMedCrossRefGoogle Scholar
  2. 2.
    O’Donnell HC, Rosand J, Knudsen KA, Furie KL, Segal AZ, Chiu RI et al (2000) Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. N Engl J Med 342:240–245PubMedCrossRefGoogle Scholar
  3. 3.
    Lee KY, Bae HG, Yun IG (1990) Recurrent intracerebral hemorrhage due to hypertension. Neurosurgery 26:586–590PubMedCrossRefGoogle Scholar
  4. 4.
    Hirohata T, Sasaki U, Uozumi T, Ohta M, Shinohara S, Takeda T et al (1991) Study on recurrence of hypertensive intracerebral hemorrhage. Neurol Med Chir (Tokyo) 31:887–891CrossRefGoogle Scholar
  5. 5.
    Chen ST, Chiang CY, Hsu CY, Lee TH, Tang LM (1995) Recurrent hypertensive intracerebral hemorrhage. Acta Neurol Scand 91:128–132PubMedCrossRefGoogle Scholar
  6. 6.
    Maruishi M, Shima T, Okada Y, Nishida M, Yamane K, Okita S (1995) Clinical findings in patients with recurrent intracerebral hemorrhage. Surg Neurol 44:444–449PubMedCrossRefGoogle Scholar
  7. 7.
    Misra UK, Kalita J (1995) Recurrent hypertensive intracerebral hemorrhage. Am J Med Sci 310:156–157PubMedCrossRefGoogle Scholar
  8. 8.
    Samani NJ, Thompson JR, O’Toole L, Channer K, Woods KL (1996) A meta-analysis of the association of the deletion allele of the angiotensin-converting enzyme gene with myocardial infarction. Circulation 94:708–712PubMedCrossRefGoogle Scholar
  9. 9.
    Sharma P (1998) Meta-analysis of the ACE gene in ischemic stroke. J Neurol Neurosurg Psychiatry 64:227–230PubMedCrossRefGoogle Scholar
  10. 10.
    Pitt B (1994) Angiotensin-converting enzyme inhibitors in patients with coronary atherosclerosis. Am Heart J 128:1328–1332PubMedCrossRefGoogle Scholar
  11. 11.
    Bianchi G (2005) Genetic variations of tubular sodium reabsorption leading to ‘primary’ hypertension: from gene polymorphism to clinical symptoms. Am J Physiol Regul Integr Comp Physiol 289:R1536–R1549PubMedCrossRefGoogle Scholar
  12. 12.
    Cusi D, Barlassina C, Azzani T, Casari G, Citterio L, Devoto M et al (1997) Polymorphisms of alpha-ADDUCIN and salt sensitivity in patients with essential hypertension. Lancet 349:1353–1357PubMedCrossRefGoogle Scholar
  13. 13.
    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 63:359–361PubMedCrossRefGoogle Scholar
  14. 14.
    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 412:642–646PubMedCrossRefGoogle Scholar
  15. 15.
    Kalita J, Misra UK, Bindu IS, Kumar B, Mittal B (2011) Angiotensin-converting enzyme (rs4646994) and αADDUCIN (rs4961) gene polymorphisms’ study in primary spontaneous intracerebral hemorrhage. Neurol India 59:41–46PubMedCrossRefGoogle Scholar
  16. 16.
    Miller S, Dykes D (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215–1219PubMedCrossRefGoogle Scholar
  17. 17.
    Lea RA, Ovcaric M, Sundholm J, Solyom L, Macmillan J, Griffiths LR (2005) Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate reductase may act in combination to increase migraine susceptibility. Brain Res Mol Brain Res 136:112–117PubMedCrossRefGoogle Scholar
  18. 18.
    Morrison AC, Doris PA, Folsom AR, Nieto FJ, Boerwinkle E (2001) Atherosclerosis Risk in Communities Study. G-protein beta3 subunit and alpha-ADDUCIN polymorphisms and risk of subclinical and clinical stroke. Stroke 32:822–829PubMedCrossRefGoogle Scholar
  19. 19.
    Kase CS (1986) Intracerebral hemorrhage: non-hypertensive causes. Stroke 17:590–595PubMedCrossRefGoogle Scholar
  20. 20.
    Broderick J, Brott T, Tomsick T, Leach A (1993) Lobar hemorrhage in the elderly. The undiminishing importance of hypertension. Stroke 24:49–51PubMedCrossRefGoogle Scholar
  21. 21.
    Passero S, Burgalassi L, Dändrea P, Battistini N (1995) Recurrence of bleeding in patients with primary intracerebral hemorrhage. Stroke 26:1189–1192PubMedCrossRefGoogle Scholar
  22. 22.
    Neau JP, Ingrand P, Couderq C, Rosier MP, Bailbe M, Dumas P et al (1997) Recurrent intracerebral hemorrhage. Neurology 49:106–113PubMedCrossRefGoogle Scholar
  23. 23.
    Gonza′lez-Duarte A, Cantu C, Rui′z-Sandoval JL, Barinagarrementeria F (1998) Recurrent primary cerebral hemorrhage frequency, mechanisms, and prognosis. Stroke 29:1802–1805CrossRefGoogle Scholar
  24. 24.
    Pitt B (1994) Angiotensin-converting enzyme inhibitors in patients with coronary atherosclerosis. Am Heart J 128:1328–1332PubMedCrossRefGoogle Scholar
  25. 25.
    Catto A, Carter AM, Barrett JH, Stickland M, Bamford J, Davies JA et al (1996) Angiotensin-converting enzyme insertion/deletion polymorphism and cerebrovascular disease. Stroke 27:435–440PubMedCrossRefGoogle Scholar
  26. 26.
    Sharma P (1998) Meta-analysis of the ACE gene in ischaemic stroke. J Neurol Neurosurg Psychiatry 64:227–230PubMedCrossRefGoogle Scholar
  27. 27.
    Dou XF, Zhang HY, Huang XH, Liu XN, Ju ZY, Sun K et al (2004) Alpha-ADDUCIN gene G/W460 polymorphism is associated with intracerebral hemorrhage in Chinese. Zhonghua Yi Xue Za Zhi 84:186–188PubMedGoogle Scholar
  28. 28.
    Zafarmand MH, Schouw YT, Grobbee DE, de Leeuw PW, Bots ML (2008) ADDUCIN Gly460Trp variant increases the risk of stroke in hypertensive Dutch women. Hypertension 51:1665–1670PubMedCrossRefGoogle Scholar
  29. 29.
    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 21:136–141PubMedCrossRefGoogle Scholar
  30. 30.
    Jeunemaitre X (2008) Genetics of the human renin angiotensin system. J Mol Med 86:637–641PubMedCrossRefGoogle Scholar
  31. 31.
    Rudnicki M, Mayer G (2009) Significance of genetic polymorphisms of the renin–angiotensin–aldosterone system in cardiovascular and renal disease. Pharmacogenomics 10:463–476PubMedCrossRefGoogle Scholar
  32. 32.
    Lee M, Saver JL, Chang KH, Liao HW, Chang SC, Ovbiagele B (2010) Impact of microalbuminuria on incident stroke: a meta-analysis. Stroke 41:2625–2631PubMedCrossRefGoogle Scholar
  33. 33.
    Cheung N, Mosley T, Islam A, Kawasaki R, Sharrett AR, Klein R et al (2010) Retinal microvascular abnormalities and subclinical magnetic resonance imaging brain infarct: a prospective study. Brain 133:1987–1993PubMedCrossRefGoogle Scholar
  34. 34.
    Pedrinelli R, Dell’Omo G, Penno G, Di Bello V, Pucci L, Fotino C et al (2006) Alpha-ADDUCIN and angiotensin-converting enzyme polymorphisms in hypertension: evidence for a joint influence on albuminuria. J Hypertension 24:931–937CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Usha K. Misra
    • 1
  • Jayantee Kalita
    • 1
  • Bindu I. Somarajan
    • 1
  • Bishwanath Kumar
    • 1
  • Moromi Das
    • 1
  • Balraj Mittal
    • 1
    • 2
  1. 1.Department of NeurologySanjay Gandhi Post Graduate Institute of Medical SciencesLucknowIndia
  2. 2.Department of Medical GeneticsSanjay Gandhi Post Graduate Institute of Medical SciencesLucknowIndia

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