Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 2000 Jul;37(7):498–500. doi: 10.1136/jmg.37.7.498

The ACE I allele is associated with increased risk for ruptured intracranial aneurysms

M Keramatipour 1, R McConnell 1, P Kirkpatrick 1, S Tebbs 1, R Furlong 1, D Rubinsztein 1
PMCID: PMC1734634  PMID: 10882751

Abstract

Genetic and environmental factors play roles in the aetiology of ruptured intracranial aneurysms. Hypertension has been reported as a risk factor for intracranial aneurysm haemorrhage. We have tested if genotypes at the angiotensin converting enzyme (ACE) gene locus are associated with ruptured intracranial aneurysms. The insertion/deletion polymorphism in the ACE gene was genotyped in 258 subjects presenting in East Anglia with ruptured intracranial aneurysms (confirmed at surgery or angiographically) and 299 controls from the same region. ACE allele frequencies were significantly different in the cases and the controls (alleles χ21=4.67, p=0.03). The I allele was associated with aneurysm risk (odds ratio for I allele v D allele = 1.3 (95% CI=1.02-1-65); odds ratio for II v DD genotype = 1.67 (95% CI=1.04-2.66)). The I allele at the ACE locus is over-represented in subjects with ruptured intracranial aneurysms. These data are supported by non-significant trends in the same direction in two previous smaller studies. Thus, this allele may be associated with risk for ruptured intracranial aneurysms.


Keywords: ACE I allele; ruptured intracranial aneurysms

Full Text

The Full Text of this article is available as a PDF (117.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alberts M. J., Quinones A., Graffagnino C., Friedman A., Roses A. D. Risk of intracranial aneurysms in families with subarachnoid hemorrhage. Can J Neurol Sci. 1995 May;22(2):121–125. doi: 10.1017/s0317167100040191. [DOI] [PubMed] [Google Scholar]
  2. Bromberg J. E., Rinkel G. J., Algra A., Greebe P., van Duyn C. M., Hasan D., Limburg M., ter Berg H. W., Wijdicks E. F., van Gijn J. Subarachnoid haemorrhage in first and second degree relatives of patients with subarachnoid haemorrhage. BMJ. 1995 Jul 29;311(7000):288–289. doi: 10.1136/bmj.311.7000.288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Butler W. E., Barker F. G., 2nd, Crowell R. M. Patients with polycystic kidney disease would benefit from routine magnetic resonance angiographic screening for intracerebral aneurysms: a decision analysis. Neurosurgery. 1996 Mar;38(3):506–516. doi: 10.1097/00006123-199603000-00018. [DOI] [PubMed] [Google Scholar]
  4. Cambien F., Costerousse O., Tiret L., Poirier O., Lecerf L., Gonzales M. F., Evans A., Arveiler D., Cambou J. P., Luc G. Plasma level and gene polymorphism of angiotensin-converting enzyme in relation to myocardial infarction. Circulation. 1994 Aug;90(2):669–676. doi: 10.1161/01.cir.90.2.669. [DOI] [PubMed] [Google Scholar]
  5. Catto A., Carter A. M., Barrett J. H., Stickland M., Bamford J., Davies J. A., Grant P. J. Angiotensin-converting enzyme insertion/deletion polymorphism and cerebrovascular disease. Stroke. 1996 Mar;27(3):435–440. [PubMed] [Google Scholar]
  6. De Braekeleer M., Pérusse L., Cantin L., Bouchard J. M., Mathieu J. A study of inbreeding and kinship in intracranial aneurysms in the Saguenay Lac-Saint-Jean region (Quebec, Canada). Ann Hum Genet. 1996 Mar;60(Pt 2):99–104. doi: 10.1111/j.1469-1809.1996.tb01181.x. [DOI] [PubMed] [Google Scholar]
  7. Dzau V. J. Cell biology and genetics of angiotensin in cardiovascular disease. J Hypertens Suppl. 1994 Jul;12(4):S3–10. [PubMed] [Google Scholar]
  8. Evans A. E., Poirier O., Kee F., Lecerf L., McCrum E., Falconer T., Crane J., O'Rourke D. F., Cambien F. Polymorphisms of the angiotensin-converting-enzyme gene in subjects who die from coronary heart disease. Q J Med. 1994 Apr;87(4):211–214. [PubMed] [Google Scholar]
  9. Falkenhahn M., Gohlke P., Paul M., Stoll M., Unger T. The renin-angiotensin system in the heart and vascular wall: new therapeutic aspects. J Cardiovasc Pharmacol. 1994;24 (Suppl 2):S6–13. [PubMed] [Google Scholar]
  10. Galinsky D., Tysoe C., Brayne C. E., Easton D. F., Huppert F. A., Dening T. R., Paykel E. S., Rubinsztein D. C. Analysis of the apo E/apo C-I, angiotensin converting enzyme and methylenetetrahydrofolate reductase genes as candidates affecting human longevity. Atherosclerosis. 1997 Mar 21;129(2):177–183. doi: 10.1016/s0021-9150(96)06027-3. [DOI] [PubMed] [Google Scholar]
  11. Iwai N., Ohmichi N., Nakamura Y., Kinoshita M. DD genotype of the angiotensin-converting enzyme gene is a risk factor for left ventricular hypertrophy. Circulation. 1994 Dec;90(6):2622–2628. doi: 10.1161/01.cir.90.6.2622. [DOI] [PubMed] [Google Scholar]
  12. Kassell N. F., Torner J. C., Haley E. C., Jr, Jane J. A., Adams H. P., Kongable G. L. The International Cooperative Study on the Timing of Aneurysm Surgery. Part 1: Overall management results. J Neurosurg. 1990 Jul;73(1):18–36. doi: 10.3171/jns.1990.73.1.0018. [DOI] [PubMed] [Google Scholar]
  13. Kehoe P. G., Russ C., McIlory S., Williams H., Holmans P., Holmes C., Liolitsa D., Vahidassr D., Powell J., McGleenon B. Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease. Nat Genet. 1999 Jan;21(1):71–72. doi: 10.1038/5009. [DOI] [PubMed] [Google Scholar]
  14. Knekt P., Reunanen A., Aho K., Heliövaara M., Rissanen A., Aromaa A., Impivaara O. Risk factors for subarachnoid hemorrhage in a longitudinal population study. J Clin Epidemiol. 1991;44(9):933–939. doi: 10.1016/0895-4356(91)90056-f. [DOI] [PubMed] [Google Scholar]
  15. Kupari M., Perola M., Koskinen P., Virolainen J., Karhunen P. J. Left ventricular size, mass, and function in relation to angiotensin-converting enzyme gene polymorphism in humans. Am J Physiol. 1994 Sep;267(3 Pt 2):H1107–H1111. doi: 10.1152/ajpheart.1994.267.3.H1107. [DOI] [PubMed] [Google Scholar]
  16. Leblanc R., Melanson D., Tampieri D., Guttmann R. D. Familial cerebral aneurysms: a study of 13 families. Neurosurgery. 1995 Oct;37(4):633–639. doi: 10.1227/00006123-199510000-00005. [DOI] [PubMed] [Google Scholar]
  17. Linz W., Wiemer G., Gohlke P., Unger T., Schölkens B. A. Contribution of kinins to the cardiovascular actions of angiotensin-converting enzyme inhibitors. Pharmacol Rev. 1995 Mar;47(1):25–49. [PubMed] [Google Scholar]
  18. O'Byrne S., Caulfield M. Genetics of hypertension. Therapeutic implications. Drugs. 1998 Aug;56(2):203–214. doi: 10.2165/00003495-199856020-00004. [DOI] [PubMed] [Google Scholar]
  19. Rigat B., Hubert C., Alhenc-Gelas F., Cambien F., Corvol P., Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990 Oct;86(4):1343–1346. doi: 10.1172/JCI114844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rosatto N., Pontremoli R., De Ferrari G., Ravazzolo R. Intron 16 insertion of the angiotensin converting enzyme gene and transcriptional regulation. Nephrol Dial Transplant. 1999 Apr;14(4):868–871. doi: 10.1093/ndt/14.4.868. [DOI] [PubMed] [Google Scholar]
  21. Schievink W. I., Limburg M., Oorthuys J. W., Fleury P., Pope F. M. Cerebrovascular disease in Ehlers-Danlos syndrome type IV. Stroke. 1990 Apr;21(4):626–632. doi: 10.1161/01.str.21.4.626. [DOI] [PubMed] [Google Scholar]
  22. Schievink W. I., Wijdicks E. F., Parisi J. E., Piepgras D. G., Whisnant J. P. Sudden death from aneurysmal subarachnoid hemorrhage. Neurology. 1995 May;45(5):871–874. doi: 10.1212/wnl.45.5.871. [DOI] [PubMed] [Google Scholar]
  23. Schächter F., Faure-Delanef L., Guénot F., Rouger H., Froguel P., Lesueur-Ginot L., Cohen D. Genetic associations with human longevity at the APOE and ACE loci. Nat Genet. 1994 Jan;6(1):29–32. doi: 10.1038/ng0194-29. [DOI] [PubMed] [Google Scholar]
  24. Takenaka K., Yamakawa H., Sakai H., Yoshimura S., Murase S., Okumura A., Nakatani K., Kimura T., Nishimura Y., Yoshimi N. Angiotensin I-converting enzyme gene polymorphism in intracranial saccular aneurysm individuals. Neurol Res. 1998 Oct;20(7):607–611. doi: 10.1080/01616412.1998.11740571. [DOI] [PubMed] [Google Scholar]
  25. Taylor C. L., Yuan Z., Selman W. R., Ratcheson R. A., Rimm A. A. Cerebral arterial aneurysm formation and rupture in 20,767 elderly patients: hypertension and other risk factors. J Neurosurg. 1995 Nov;83(5):812–819. doi: 10.3171/jns.1995.83.5.0812. [DOI] [PubMed] [Google Scholar]
  26. Todd J. A. Interpretation of results from genetic studies of multifactorial diseases. Lancet. 1999 Jul;354 (Suppl 1):SI15–SI16. doi: 10.1016/s0140-6736(99)90243-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES