TY - JOUR
T1 - Deletion/insertion polymorphism of the angiotensin-converting enzyme gene and white matter hyperintensities in dementia: A pilot study
AU - Purandare, Nitin
AU - Oude Voshaar, Richard C.
AU - Davidson, Yvonne
AU - Gibbons, Linda
AU - Hardicre, Jayne
AU - Byrne, Jane
AU - McCollum, Charles
AU - Jackson, Alan
AU - Burns, Alistair
AU - Mann, David M A
PY - 2006/9
Y1 - 2006/9
N2 - OBJECTIVES: To examine the association between the angiotensin-converting enzyme (ACE) deletion/insertion (D/I) polymorphism and white matter hyperintensities (WMHs) in patients with dementia. DESIGN: Observational pilot study with adjustment for potential confounders using analysis of covariance. SETTING: Secondary care old-age psychiatry services in greater Manchester, United Kingdom. PARTICIPANTS: Ninety-seven patients with dementia: 49 with Alzheimer's disease (AD, National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria) and 48 with vascular dementia (VaD, National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria). MEASUREMENTS: The ACE D/I polymorphism, WMHs (deep WMHs (DWMHs) and periventricular hyperintensities (PVHs)) on T2-weighted magnetic resonance imaging, and potential cardiovascular confounders. RESULTS: The D/D polymorphism of the ACE genotype was associated with severity of DWMH (P=.005) but not PVH (P=.34), corrected for age, cardiovascular risk factors, and type of dementia. Post hoc analyses were limited by statistical power but suggested an interaction with the apolipoprotein E ε4 allele. CONCLUSION: The results support previous observations that genetic factors influence the development of WMHs in dementia. The involvement of the ACE D/I polymorphism in the pathogenesis of DWMHs in dementia (AD and VaD), by a mechanism that is independent of its association with cardiovascular risk factors, should be confirmed in a large population-based sample. © 2006, Copyright the Authors.
AB - OBJECTIVES: To examine the association between the angiotensin-converting enzyme (ACE) deletion/insertion (D/I) polymorphism and white matter hyperintensities (WMHs) in patients with dementia. DESIGN: Observational pilot study with adjustment for potential confounders using analysis of covariance. SETTING: Secondary care old-age psychiatry services in greater Manchester, United Kingdom. PARTICIPANTS: Ninety-seven patients with dementia: 49 with Alzheimer's disease (AD, National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria) and 48 with vascular dementia (VaD, National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria). MEASUREMENTS: The ACE D/I polymorphism, WMHs (deep WMHs (DWMHs) and periventricular hyperintensities (PVHs)) on T2-weighted magnetic resonance imaging, and potential cardiovascular confounders. RESULTS: The D/D polymorphism of the ACE genotype was associated with severity of DWMH (P=.005) but not PVH (P=.34), corrected for age, cardiovascular risk factors, and type of dementia. Post hoc analyses were limited by statistical power but suggested an interaction with the apolipoprotein E ε4 allele. CONCLUSION: The results support previous observations that genetic factors influence the development of WMHs in dementia. The involvement of the ACE D/I polymorphism in the pathogenesis of DWMHs in dementia (AD and VaD), by a mechanism that is independent of its association with cardiovascular risk factors, should be confirmed in a large population-based sample. © 2006, Copyright the Authors.
KW - ACE polymorphism
KW - Dementia
KW - White matter lesions
U2 - 10.1111/j.1532-5415.2006.00841.x
DO - 10.1111/j.1532-5415.2006.00841.x
M3 - Article
SN - 1532-5415
VL - 54
SP - 1395
EP - 1400
JO - Journal of the American Geriatrics Society
JF - Journal of the American Geriatrics Society
IS - 9
ER -
