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J Med Genet 2000;37:695-697 doi:10.1136/jmg.37.9.695
  • Short report

The ACE gene and Alzheimer's disease susceptibility

  1. Yolanda Naraina,
  2. Agustin Yipa,b,
  3. Terence Murphya,
  4. Carol Brayneb,
  5. Douglas Eastonc,
  6. John Grimley Evansd,
  7. John Xuerebe,
  8. Nigel Cairnsf,
  9. Margaret M Esirig,
  10. Robert A Furlonga,
  11. David C Rubinszteina
  1. aDepartment of Medical Genetics, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK, bDepartment of Public Health and Primary Care, University Forvie Site, Robinson Way, Cambridge CB2 2SR, UK, cCRC Genetic Epidemiology Unit, Cambridge University Department of Public Health and Primary Care, Strangeways Research Laboratory, Wort's Causeway, Cambridge CB1 8RN, UK, dDepartment of Clinical Geratology, Radcliffe Infirmary, Oxford OX2 6HE, UK, eDepartment of Pathology, Cambridge University, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK, fMedical Research Council Brain Bank, Department of Neuropathology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK, gNeuropathology Department, Radcliffe Infirmary, Oxford OX2 6HE, UK
  1. Dr Rubinsztein, dcr1000{at}cus.cam.ac.uk
  • Revised 19 April 2000
  • Accepted 3 May 2000

Abstract

A recent study suggested that the insertion (I) allele in intron 16 of the angiotensin converting enzyme gene (ACE) is associated with Alzheimer's disease (AD) risk. In our series of 239 necropsy confirmed late onset AD cases and 342 elderly non-demented controls aged >73 years, we found significantly different ACE genotype distributions in the case and control groups (p=0.007). Homozygotes for both the I and D alleles were associated with a higher risk compared to DI heterozygotes. While the APOEε4 allele was strongly associated with AD risk in our series, we found no evidence for an interaction between theAPOE andACE loci. In addition, no interactions were observed between ACE and gender or age at death of the AD cases. A meta-analysis of all published reports (12 case-control series in total) suggested that both the II and IDACE genotypes are associated with increased AD risk (odds ratio (OR) for II v DD 1.36, 95% confidence interval (CI)=1.13-1.63, OR for DIv DD 1.33, 95% CI=1.14-1.53, p=0.0002).

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