Deletion/insertion polymorphism of the angiotensin-converting enzyme gene and white matter hyperintensities in dementia: A pilot study.
OBJECTIVE
To examine the association between the angiotensin-converting enzyme (ACE) deletion/insertion (D/I) polymorphism and white matter hyperintensities (WMHs) in patients with dementia.


METHODS
Observational pilot study with adjustment for potential confounders using analysis of covariance.


METHODS
Secondary care old-age psychiatry services in greater Manchester, United Kingdom.


METHODS
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).


METHODS
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 epsilon4 allele.


CONCLUSIONS
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.
Purandare
Nitin
N
Division of Psychiatry, Education and Research Center, South Manchester University Hospital, Manchester, United Kingdom. nitin.purandare@manchester.ac.uk
Oude Voshaar
Richard C
RC
Davidson
Yvonne
Y
Gibbons
Linda
L
Hardicre
Jayne
J
Byrne
Jane
J
McCollum
Charles
C
Jackson
Alan
A
Burns
Alistair
A
Mann
David M A
DM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000473:pathology*; D015140:Dementia, Vascular / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010865:Pilot Projects; D011110:Polymorphism, Genetic / Q000235:genetics*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D007703:Peptidyl-Dipeptidase A