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Association of ACE gene I/D polymorphism and ACE levels with hemorrhagic stroke: comparison with ischemic stroke

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Abstract

In the present study, we investigated the association of insertion/deletion polymorphism of ACE gene with genetic predisposition to hemorrhagic stroke and also determined the mean ACE activity levels in ischemic and hemorrhagic stroke patients. Two hundred hemorrhagic stroke, 200 ischemic stroke patients and 200 gender and age matched controls were recruited for the study. We found statistically significant difference in the genotypic distribution between hemorrhagic patients and controls for dominant, co-dominant and recessive models. Significant difference was observed in the allelic frequencies between hemorrhagic patients and controls. Multiple logistic regression analysis confirmed these findings [adjusted OR for DD genotype was 2.46 (95 % CI 1.43–4.21) and p = 0.001] and [adjusted OR for ID genotype was 5.45 (95 % CI 2.6–10.4) and p = 0.001]. We have already established the association of this polymorphism in ischemic stroke patients. Comparing hemorrhagic with ischemic stroke, we found a significant difference in genotypic distribution between the two [for II vs. DD, χ 2 = 4.75; p = 0.03, OR = 0.5 (95 % CI 0.27–0.93) and for DD vs. ID, χ 2 = 5.1; p = 0.02, OR = 1.8 (95 % CI 1.1–3.3)]. Our results indicate that DD genotype and D allele are important risk factors for the development of stroke. Individuals harboring DD genotype of ACE I/D polymorphism are more predisposed to hemorrhagic stroke than ischemic stroke. Further, the mean ACE activity level was found to be significantly higher in hemorrhagic and ischemic stroke in comparison with controls, but there was no significant difference in the levels found between the two types of stroke.

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References

  1. Rosamond WD, Folsom AR, Chambless LE (1999) Stroke incidence and survival among middle aged adults: 9-year follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort. Stroke 30(4):736–743

    Article  CAS  PubMed  Google Scholar 

  2. Alberts MJ (2003) Stroke genetics update. Stroke 34:342–344

    Article  PubMed  Google Scholar 

  3. Feigin V, Lawes C, Bennet D, Barker Cello S, Parag V (2009) Worldwide stroke incidence and early case fatality in 56 population based studies: a systematic review. Lancet Neurol 8(4):355–369

    Article  PubMed  Google Scholar 

  4. Alberts MJ, McCarron MO, Hoffmann KL, Graffagnino C (2002) Familial clustering of intracerebral hemorrhage: a prospective study in North Carolina. Neuroepidemiology 21(1):18–21

    Article  CAS  PubMed  Google Scholar 

  5. Casas JP, Hingorani AD, Bautista LE, Sharma P (2004) Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. Arch Neurol 61(11):1652–1661

    Article  PubMed  Google Scholar 

  6. Erdos EG, Skidgel RA (1987) The angiotensin I-converting enzyme. Lab Invest 56:345–348

    CAS  PubMed  Google Scholar 

  7. Crisan D, Carr J (2000) Angiotensin I-converting enzyme: genotype and disease associations. J Mol Diagn 2:105–115

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. 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 86:1343–1346

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Pera J, Slowik A, Dziedzic T, Wloch D, Szczudlik A (2006) ACE I/D polymorphism in different etiologies of ischemic stroke. Acta Neurol Scand 114(5):320–322

    Article  CAS  PubMed  Google Scholar 

  10. Tuncer N, Tuglular S, Kilic G, Sazci A, Us O, Kara I (2006) Evaluation of the angiotensin-converting enzyme insertion/deletion polymorphism and the risk of ischaemic stroke. J Clin Neurosci 13(2):224–227

    Article  CAS  PubMed  Google Scholar 

  11. Szolnoki Z, Maasz A, Magyari L (2006) Coexistence of angiotensin II type-1 receptor A1166C and angiotensin converting enzyme D/D polymorphism suggests susceptibility for small-vessel-associated ischemic stroke. Neuro Mol Med 8(3):353–360

    Article  CAS  Google Scholar 

  12. Munshi A, Sultana S, Kaul S, Reddy PB, Alladi S, Jyothy A (2008) Angiotensin-converting enzyme insertion/deletion polymorphism and the risk of ischemic stroke in a South Indian population. J Neurol Sci 272:132–135

    Article  CAS  PubMed  Google Scholar 

  13. Hong SH, Park HM, Ahn JY, Kim OJ, Hwang TS, Oh D, Kim NK (2008) ACE I/D polymorphism in Korean patients with ischemic stroke and silent brain infarction. Acta Neurol Scand 117(4):244–249

    Article  CAS  PubMed  Google Scholar 

  14. Raynolds MV, Bristow MR, Bush EW, Abraham WT, Lowers BD, Zisman LS (1993) Angiotensin-converting enzyme DD genotype in patients with ischemic or idiopathic cardiomyopathy. Lancet 342:1073–1075

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  16. Staalso JM, Nielsen M, Edsen T (2011) Common variants of the ACE gene and aneurysmal subarachnoid hemorrhage in a Danish population: a case–control study. J Neurosurg Anesthesiol 23:304–309

    Article  PubMed  Google Scholar 

  17. Slowik A, Turaj W, Dziedzic T (2004) DD genotype of ACE gene is a risk factor for intracerebral hemorrhage. Neurology 63:359–361

    Article  CAS  PubMed  Google Scholar 

  18. Dardiotis E, Jagiella J, Xiromerisiou G (2011) Angiotensin-converting enzyme tag single nucleotide polymorphisms in patients with intracerebral hemorrhage. Pharmacogenet Genomics 21:136–141

    Article  CAS  PubMed  Google Scholar 

  19. Rudijanto A (2007) The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis. Acta Med Indones 39(2):152–160

    Google Scholar 

  20. Engeli S, Negrel R, Sharma AM (2000) Physiology and pathology of the adipose tissue renin–angiotensin system. Hypertension 35:1270–1277

    Article  CAS  PubMed  Google Scholar 

  21. Karsito, Soeatmadji DW (2008) Diabetes and stroke. Acta Med Indones 40(3):128–140

    Google Scholar 

  22. Higaki J, Baba S, Katsuya T, Sato N, Ishikawa K, Mannami T (2000) Deletion allele of angiotensin-converting enzyme gene increases risk of essential hypertension in Japanese men. Circulation 101:2060–2065

    Article  CAS  PubMed  Google Scholar 

  23. Brott T, Thalinger K, Hertzberg V (1986) Hypertension as a risk factor for spontaneous intracerebral hemorrhage. Stroke 17:1078–1083

    Article  CAS  PubMed  Google Scholar 

  24. Johanning GL, Johnston KE, Tamura T, Goldenberg RL (1995) Ethnic differences in angiotensin converting enzyme gene polymorphism. J Hypertens 13:710–711

    Article  CAS  PubMed  Google Scholar 

  25. Ariesen MJ, Claus SP, Rinkel GJ, Algra A (2003) Risk factors for intracerebral hemorrhage in the general population: a systematic review. Stroke 34:2060–2065

    Article  CAS  PubMed  Google Scholar 

  26. Sun Y, Ye Liu Y, Watts LT, Sun Q, Zhong Z, Yang GY (2013) Genetic associations of angiotensin-converting enzyme with primary intracerebral hemorrhage: a meta-analysis. PLoS ONE 8(6):e67402

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Huang Y, Li G, Lan H, Zhao GY, Huang CZ (2013) Angiotensin-converting enzyme insertion/deletion gene polymorphisms and risk of intracerebral hemorrhage: a meta-analysis of epidemiologic studies. J Renin Angiotensin Aldosterone Syst 3:1–7

    Google Scholar 

  28. 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 522:196–205

    Article  CAS  PubMed  Google Scholar 

  29. Tiret L, Rigat B, Visvikis S, Breda C, Corvol P (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

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Danser AH, Schalekamp MA, Bax WA, van den Brink AM, Saxena PR (1995) Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation 2:1387–1388

    Article  Google Scholar 

  31. Catto A, Carter AM, Barrett JH, Stickland M, Bamford J, Davies JA, Grant PJ (1996) Angiotensin-converting enzyme insertion/deletion polymorphism and cerebrovascular disease. Stroke 27:435–440

    Article  CAS  PubMed  Google Scholar 

  32. Juo SH (2009) Genetics of carotid atherosclerosis. Front Biosci 14:4525–4534

    Article  CAS  Google Scholar 

  33. Daemen MJ, Lombardi DM, Bosman FT, Schwartz SM (1991) Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ Res 68:450–456

    Article  CAS  PubMed  Google Scholar 

  34. Fleming I (2006) Signaling by the angiotensin-converting enzyme. Circ Res 98:887–896

    Article  CAS  PubMed  Google Scholar 

  35. Castro-Chaves P, Cerqueira R, Pintalhao M, Leite-Moreira AF (2010) New pathways of the renin–angiotensin system: the role of ACE2 in cardiovascular pathophysiology and therapy. Expert Opin Ther Targets 5:485–496

    Article  Google Scholar 

  36. Vaajanen A, Vapaatalo H (2010) Local ocular renin–angiotensin system—a target for glaucoma therapy? Basic Clin Pharmacol Toxicol 109:217–224

    Article  Google Scholar 

  37. Misra UK, Kalita J, Somarajan BI (2012) Do ACE (rs4646994) and alphaADDUCIN (rs4961) gene polymorphisms predict the recurrence of hypertensive intracerebral hemorrhage? Neurol Sci 33:1071–1077

    Article  PubMed  Google Scholar 

  38. Chen CM, Chen YC, Wu YR (2008) Angiotensin-converting enzyme polymorphisms and risk of spontaneous deep intracranial hemorrhage in Taiwan. Eur J Neurol 15:1206–1211

    Article  PubMed  Google Scholar 

  39. Domingues-Montanari S, Hernandez-Guillamon M, Fernan-dez-Cadenas I (2011) ACE variants and risk of intracerebral hemorrhage recurrence in amyloid angiopathy. Neurobiol Aging 32(551):e513–e522

    Google Scholar 

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Correspondence to Anjana Munshi.

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Das, S., Roy, S., Sharma, V. et al. Association of ACE gene I/D polymorphism and ACE levels with hemorrhagic stroke: comparison with ischemic stroke. Neurol Sci 36, 137–142 (2015). https://doi.org/10.1007/s10072-014-1880-8

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  • DOI: https://doi.org/10.1007/s10072-014-1880-8

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