Journal of Molecular Neuroscience

, Volume 28, Issue 3, pp 285–290 | Cite as

Angiotensin II type-1 receptor A1166C polymorphism is associated with increased risk of ischemic stroke in hypertensive smokers

  • Zoltán Szolnoki
  • Viktória Havasi
  • Gábor Talián
  • Judit Bene
  • Katalin Komlósi
  • Ferenc Somogyvári
  • András Kondacs
  • Mihály Szabó
  • Lajos Fodor
  • Anita Bodor
  • Béla Melegh
Original Article

Abstract

Recent observations revealed a novel role of angiotensin-converting enzyme 2 and the angiotensin II type-1 receptor (AT1R) in lung injury, thereby extending knowledge about the functions of the angiotensin system. Angiotensin II, whose target is the AT1R, is a potent vasoconstrictor. Accordingly, an imbalance leading to enhanced activity of the angiotensin II-AT1R axis is postulated to contribute to both circulatory disturbances and lung injury. In this context, a functional single-nucleotide polymorphism, AT1R A1166C, which leads to enhanced responsiveness of the AT1R, has been postulated as a candidate susceptibility factor for ischemic stroke. The aim of our study was to investigate its occurrence in ischemic stroke and to analyze its possible synergistic associations with clinical risk factors. Genetic and clinical data on 308 consecutive patients with acutely developing ischemic stroke were analyzed. A total of 272 stroke and neuroimaging alteration-free subjects served as a control group. Univariate and logistic regression statistical approaches were used. Alone, the AT1R 1166C allele did not pose a risk of stroke. In hypertensive smokers, however, it was associated with an increased risk of ischemic stroke (OR 22.3, 95% CI 5.8–110.2, p<0.001). Further subgroup analysis revealed the same association for both small-vessel (OR 24.3, 95% CI 6.1–121.1, p<0.001) and large-vessel (OR 21.3, 95% CI 4.6–81.1, p<0.001) infarction. On a pathophysiological basis, our results suggest the possibility that the AT1R A1166C polymorphism might give rise to ischemic stroke indirectly via an unfavorable effect on the cardiorespiratory function.

Index Entries

AT1R A1166C polymorphism stroke risk genetic interaction 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agachan B., Isbir T., Yilmaz H., and Akoglu E. (2003) Angiotensin converting enzyme I/D, angiotensinogen T174M-M235T and angiotensin II type 1 receptor A1166C gene polymorphisms in Turkish hypertensive patients. Exp. Mol. Med. 35, 545–549.PubMedGoogle Scholar
  2. Cheng Z. J., Vapaatalo H. and Mervaala E. (2005) Angiotensin II and vascular inflammation. Med. Sci. Monit. 25, 194–205.Google Scholar
  3. Ferreira A.J. and Santos R.A.S. (2005) Cardiovascular action of angiotensin (1–7). Braz. J. Med. Biol. Res. 38, 499–507.PubMedGoogle Scholar
  4. Fukazawa R., Sonobe T., Hamamato K., Hamaoka K., Sakata K., Asano T., et al. (2004) Possible synergic effect of angiotensin-I converting enzyme insertion/deletion polymorphism and angiotensin-II type-1 receptor 1166A/C gene polymorphism on ischaemic heart disease in patients with Kawasaki disease. Pediatr. Res. 56, 597–601.PubMedCrossRefGoogle Scholar
  5. Henderson S.O., Haiman C.A., and Mack W. (2004) Multiple polymorphisms in the renin-angiotensin-aldosterone system (ACE, CYP11B2, AGTR1) and their contribution to hypertension in African Americans and Latinos in the multiethnic cohort. Am. J. Med. Sci. 328, 266–273.PubMedCrossRefGoogle Scholar
  6. Hindorff L. A., Heckbert S. R., Tracy R., Tang Z., Psaty B. M., Edwards K. I., et al. (2002) Angiotensin II type 1 receptor polymorphisms in the cardiovascular health study: relation to blood pressure, ethnicity, and cardiovascular events. Am. J. Hypertens. 15, 1050–1056.PubMedCrossRefGoogle Scholar
  7. Imai Y., Kuba K., Rao S., Huan Y., Guo F., Guan B., et al. (2005) Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 436, 112–116.PubMedCrossRefGoogle Scholar
  8. Jones A., Dhamrait S. S., Payne J. R., Hawe E., Li P., Toor I.S., et al. (2003) Genetic variants of angiotensin II receptors and cardiovascular risk in hypertension. Hypertension 42, 500–506.PubMedCrossRefGoogle Scholar
  9. Kobashi G., Hata A., Ohta K., Yamada H., Kato E. H., Minakami H., et al. (2004) A1166C variant of angiotensin II type 1 receptor gene is associated with severe hypertension in pregnancy independently of T235 variant of angiotensinogen gene. J. Hum. Genet. 49, 182–186.PubMedCrossRefGoogle Scholar
  10. Kuba K., Imai Y., Rao S., Gao H., Guo F., Guan B., et al. (2005) A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat. Med. 11, 875–879.PubMedCrossRefGoogle Scholar
  11. Miller, J. A. and Scholey J. W. (2004) The impact of reninangiotensin system polymorphisms on physiological and pathophysiological processes in humans. Curr. Opin. Nephrol. Hypertens. 13, 101–106.PubMedCrossRefGoogle Scholar
  12. Miller S.A., Dykes D.D., and Polesky H.F. (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16, 1215–1218.PubMedCrossRefGoogle Scholar
  13. Munzel T., Daiber A., Ullrich V., and Mulsch A. (2005) Vascular consequences of endothelial nitric oxide synthase uncoupling for the activity and expression of the soluble guanylyl cyclase and the cGMP-dependent protein kinase. Arterioscler. Thromb. Vasc. Biol. 25, 1551–1557.PubMedCrossRefGoogle Scholar
  14. Nicholls J. and Peiris M. (2005) Good ACE, bad ACE do battle in lung injury, SARS. Nat. Med. 11, 821–822.PubMedCrossRefGoogle Scholar
  15. Rubattu S., DiAngelantonio E., Stanzione R., Zanda B., Evangelista A., Pirisi A., et al. (2004) Gene polymorphisms of the renin-angiotensin-aldosterone system and the risk of ischemic stroke: a role of the A1166C/AT1 gene variant. J. Hypertens. 22, 2129–2134.PubMedCrossRefGoogle Scholar
  16. Sainani G. S. and Maru V. G. (2004) Role of endothelial cell dysfunction in essential hypertension. J. Assoc. Physicians India 52, 966–969.PubMedGoogle Scholar
  17. Schmieder R. E. (2005) Mechanisms for the clinical benefits of angiotensin II receptor blockers. Am. J. Hypertens. 18, 720–730.PubMedCrossRefGoogle Scholar
  18. Schram M. T. and Stehouwer C. D. (2005) Endothelial dysfunction, cellular adhesion molecules and the metabolic syndrome. Horm. Metab. Res. 37, 49–55.PubMedCrossRefGoogle Scholar
  19. Sugimoto K., Katsuya T., Ohkubo T., Hozawa A., Yamamoto K., Matsuo A., et al. (2004) Association between angiotensin II type 1 receptor gene polymorphism and essential hypertension: the Ohasama Study. Hypertens. Res. 27, 551–556.PubMedCrossRefGoogle Scholar
  20. Szolnoki Z., Somogyvari F., Kondacs A., Szabo M., and Fodor L. (2002) Evaluation of the interactions of common genetic mutations in stroke subtypes. J. Neurol. 249, 1391–1397.PubMedCrossRefGoogle Scholar
  21. Szolnoki Z., Somogyvari F., Kondacs A., Szabo M., Fodor L., Bene J., and Melegh B. (2003) Evaluation of the modifying effects of unfavourable genotypes on classical clinical risk factors for ischaemic stroke. J. Neurol. Neurosurg. Psychiatry 74, 1615–1620.PubMedCrossRefGoogle Scholar
  22. Treszl A., Szabo M., Dunai G., Nobilis A., Kocsis I., Machay T., et al. (2003) Angiotensin II type 1 receptor, a 1166C polymorphism and prophylactic indomethacin treatment induced ductus arterious closure in very low birth weight neonates. Pediatr. Res. 54, 753–755.PubMedCrossRefGoogle Scholar
  23. Um J. Y., Moon K. S., Lee K. M., Cho K. H., Heo Y., Moon B. S., and Kim H. M. (2003) Polymorphism of angiotensin-converting enzyme, angiotensinogen, and apolipoprotein E genes in Korean patients with cerebral infaction. J. Mol. Neurosci. 21, 23–28.PubMedCrossRefGoogle Scholar
  24. van Geel P.P., Pinto Y.M., Voors A.A., Buikema H., Oosterga M., Crijns H.J.G.M., and van Gilst W. H. (2000) Angiotenin II type 1 receptor A1166C gene polymorphism is associated with an increased response to angiotensin II in human arteries. Hypertension 35, 717–721.PubMedGoogle Scholar
  25. World Health Organization (1985) Report on diabetes mellitus. World Health Organ. Tech. Rep. Ser. 727.Google Scholar

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  • Zoltán Szolnoki
    • 1
  • Viktória Havasi
    • 3
  • Gábor Talián
    • 3
  • Judit Bene
    • 4
  • Katalin Komlósi
    • 3
  • Ferenc Somogyvári
    • 2
    • 5
  • András Kondacs
    • 1
  • Mihály Szabó
    • 1
  • Lajos Fodor
    • 2
  • Anita Bodor
    • 6
  • Béla Melegh
    • 3
    • 4
  1. 1.Department of Neurology and NeurophysiologyPándy Kálmán County HospitalGyulaHungary
  2. 2.Central LaboratoryPándy Kálmán County HospitalGyulaHungary
  3. 3.Department of Medical Genetics and Child DevelopmentUniversity of PécsPécsHungary
  4. 4.MTA-PTE Clinical Genetics Research Group of Hungarian Academy of SciencesUniversity of PécsPécsHungary
  5. 5.Department of Clinical Microbiology, Faculty of MedicineUniversity of SzegedSzegedHungary
  6. 6.Department of PathologyRéthy Pál County HospitalBékéscsabaHungary

Personalised recommendations