Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2002 Mar;72(3):343–346. doi: 10.1136/jnnp.72.3.343

Angiotensin converting enzyme insertion/deletion genotype is associated with leukoaraiosis in lacunar syndromes

A Hassan 1, A Lansbury 1, A Catto 1, A Guthrie 1, J Spencer 1, C Craven 1, P Grant 1, J Bamford 1
PMCID: PMC1737772  PMID: 11861692

Abstract

Objectives: Pathological and clinical data suggest that patients presenting with ischaemic lacunar syndromes may be a heterogenous group. Those with isolated lacunar infarction are thought to have localised atherosclerosis whereas in those with coexisting leukoaraiois a distinct diffuse small vessel vasculopathy may be the predominant underlying pathology. The ACE insertion/deletion (I/D) polymorphism is an important candidate gene in ischaemic cerebrovascular disease but, where lacunar stroke specifically has been examined, there have been discrepant reports concerning a possible association. It was hypothesised that the influence of the ACE gene may be different among the two subgroups of ischaemic lacunar stroke reflecting the heterogeneity of the small vessel disease phenotype.

Methods: Eighty four consecutive patients presenting with classic lacunar syndromes were studied. All had acute cranial CT to exclude primary intracerebral haemorrhage and these were subsequently assessed for the presence and extent of leukoaraiosis. All patients were genotyped for the ACE insertion/deletion polymorphism.

Results: There was a significant difference in the distribution of ACE genotype with the DD genotype occurring more often in patients with leukoaraiosis and the II and ID genotypes occurring more often among those in whom this was absent (χ2=9.06, p=0.01). In a logistic regression model the ACE DD genotype remained as an independent predictor for the presence of leukoaraiosis (p=0.02) in patients presenting with classic lacunar syndromes.

Conclusion: This study supports the hypothesis that there may be different types of small vessel disease in patients with classic lacunar syndromes and that the influence of the ACE DD genotype may be relevant in mediating the diffuse form of vessel injury.

Full Text

The Full Text of this article is available as a PDF (105.1 KB).

Selected References

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

  1. Bamford J., Sandercock P., Jones L., Warlow C. The natural history of lacunar infarction: the Oxfordshire Community Stroke Project. Stroke. 1987 May-Jun;18(3):545–551. doi: 10.1161/01.str.18.3.545. [DOI] [PubMed] [Google Scholar]
  2. Boiten J., Lodder J., Kessels F. Two clinically distinct lacunar infarct entities? A hypothesis. Stroke. 1993 May;24(5):652–656. doi: 10.1161/01.str.24.5.652. [DOI] [PubMed] [Google Scholar]
  3. Brass L. M., Isaacsohn J. L., Merikangas K. R., Robinette C. D. A study of twins and stroke. Stroke. 1992 Feb;23(2):221–223. doi: 10.1161/01.str.23.2.221. [DOI] [PubMed] [Google Scholar]
  4. Butler R., Morris A. D., Burchell B., Struthers A. D. DD angiotensin-converting enzyme gene polymorphism is associated with endothelial dysfunction in normal humans. Hypertension. 1999 May;33(5):1164–1168. doi: 10.1161/01.hyp.33.5.1164. [DOI] [PubMed] [Google Scholar]
  5. Carmelli D., DeCarli C., Swan G. E., Jack L. M., Reed T., Wolf P. A., Miller B. L. Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins. Stroke. 1998 Jun;29(6):1177–1181. doi: 10.1161/01.str.29.6.1177. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Fassbender K., Mielke O., Bertsch T., Nafe B., Fröschen S., Hennerici M. Homocysteine in cerebral macroangiography and microangiopathy. Lancet. 1999 May 8;353(9164):1586–1587. doi: 10.1016/S0140-6736(99)00309-8. [DOI] [PubMed] [Google Scholar]
  8. Fisher C. M. Capsular infarcts: the underlying vascular lesions. Arch Neurol. 1979 Feb;36(2):65–73. doi: 10.1001/archneur.1979.00500380035003. [DOI] [PubMed] [Google Scholar]
  9. Fisher C. M. Lacunar strokes and infarcts: a review. Neurology. 1982 Aug;32(8):871–876. doi: 10.1212/wnl.32.8.871. [DOI] [PubMed] [Google Scholar]
  10. Fisher C. M. The arterial lesions underlying lacunes. Acta Neuropathol. 1968 Dec 18;12(1):1–15. doi: 10.1007/BF00685305. [DOI] [PubMed] [Google Scholar]
  11. Gustincich S., Manfioletti G., Del Sal G., Schneider C., Carninci P. A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques. 1991 Sep;11(3):298-300, 302. [PubMed] [Google Scholar]
  12. Hijdra A., Verbeeten B., Jr, Verhulst J. A. Relation of leukoaraiosis to lesion type in stroke patients. Stroke. 1990 Jun;21(6):890–894. doi: 10.1161/01.str.21.6.890. [DOI] [PubMed] [Google Scholar]
  13. Joutel A., Corpechot C., Ducros A., Vahedi K., Chabriat H., Mouton P., Alamowitch S., Domenga V., Cécillion M., Marechal E. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature. 1996 Oct 24;383(6602):707–710. doi: 10.1038/383707a0. [DOI] [PubMed] [Google Scholar]
  14. Kraus J. P., Le K., Swaroop M., Ohura T., Tahara T., Rosenberg L. E., Roper M. D., Kozich V. Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells. Hum Mol Genet. 1993 Oct;2(10):1633–1638. doi: 10.1093/hmg/2.10.1633. [DOI] [PubMed] [Google Scholar]
  15. Markus H. S., Barley J., Lunt R., Bland J. M., Jeffery S., Carter N. D., Brown M. M. Angiotensin-converting enzyme gene deletion polymorphism. A new risk factor for lacunar stroke but not carotid atheroma. Stroke. 1995 Aug;26(8):1329–1333. doi: 10.1161/01.str.26.8.1329. [DOI] [PubMed] [Google Scholar]
  16. Matsushita K., Kuriyama Y., Nagatsuka K., Nakamura M., Sawada T., Omae T. Periventricular white matter lucency and cerebral blood flow autoregulation in hypertensive patients. Hypertension. 1994 May;23(5):565–568. doi: 10.1161/01.hyp.23.5.565. [DOI] [PubMed] [Google Scholar]
  17. Mochizuki Y., Oishi M., Takasu T. Cerebral blood flow in single and multiple lacunar infarctions. Stroke. 1997 Jul;28(7):1458–1460. doi: 10.1161/01.str.28.7.1458. [DOI] [PubMed] [Google Scholar]
  18. Pullicino P., Kwen P. L., Greenberg S., Becker A. L., Glenister N. Angiotensin-converting enzyme gene and lacunar stroke. Stroke. 1996 Mar;27(3):569–570. [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. Rose G., McCartney P., Reid D. D. Self-administration of a questionnaire on chest pain and intermittent claudication. Br J Prev Soc Med. 1977 Mar;31(1):42–48. doi: 10.1136/jech.31.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Shanmugam V., Sell K. W., Saha B. K. Mistyping ACE heterozygotes. PCR Methods Appl. 1993 Oct;3(2):120–121. doi: 10.1101/gr.3.2.120. [DOI] [PubMed] [Google Scholar]
  23. van Swieten J. C., Hijdra A., Koudstaal P. J., van Gijn J. Grading white matter lesions on CT and MRI: a simple scale. J Neurol Neurosurg Psychiatry. 1990 Dec;53(12):1080–1083. doi: 10.1136/jnnp.53.12.1080. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES