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.
Similar content being viewed by others
References
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
Alberts MJ (2003) Stroke genetics update. Stroke 34:342–344
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
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
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
Erdos EG, Skidgel RA (1987) The angiotensin I-converting enzyme. Lab Invest 56:345–348
Crisan D, Carr J (2000) Angiotensin I-converting enzyme: genotype and disease associations. J Mol Diagn 2:105–115
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
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
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
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
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
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
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
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
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
Slowik A, Turaj W, Dziedzic T (2004) DD genotype of ACE gene is a risk factor for intracerebral hemorrhage. Neurology 63:359–361
Dardiotis E, Jagiella J, Xiromerisiou G (2011) Angiotensin-converting enzyme tag single nucleotide polymorphisms in patients with intracerebral hemorrhage. Pharmacogenet Genomics 21:136–141
Rudijanto A (2007) The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis. Acta Med Indones 39(2):152–160
Engeli S, Negrel R, Sharma AM (2000) Physiology and pathology of the adipose tissue renin–angiotensin system. Hypertension 35:1270–1277
Karsito, Soeatmadji DW (2008) Diabetes and stroke. Acta Med Indones 40(3):128–140
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
Brott T, Thalinger K, Hertzberg V (1986) Hypertension as a risk factor for spontaneous intracerebral hemorrhage. Stroke 17:1078–1083
Johanning GL, Johnston KE, Tamura T, Goldenberg RL (1995) Ethnic differences in angiotensin converting enzyme gene polymorphism. J Hypertens 13:710–711
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
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
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
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
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
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
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
Juo SH (2009) Genetics of carotid atherosclerosis. Front Biosci 14:4525–4534
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
Fleming I (2006) Signaling by the angiotensin-converting enzyme. Circ Res 98:887–896
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
Vaajanen A, Vapaatalo H (2010) Local ocular renin–angiotensin system—a target for glaucoma therapy? Basic Clin Pharmacol Toxicol 109:217–224
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
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
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
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10072-014-1880-8