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DOI: 10.1055/s-2007-977358
The influence of genetics on white matter lesion load in patients with vascular subcortical dementia compared to patients with Alzheimer disease and persons without cognitive impairment
Ziele: Ischemic neuronal disintegration of the brain tissue is a main risk factor for the developement of a vascular dementia (VD). Because of the complexity of cerebrovascular and other factors it is not possible to describe the whole variance of the incidence of VD merely by genetic polymorphisms. Nevertheless there is hope to identify the contribution of genetic markers in VD. Methode: Data of clinically, neuropsychologically, neuroradiologically and genetically examined patients (n=236) of a memory clinic were analysed upon the interrelation of clinical diagnosis according to ICD-10 and genetics, differentiated in the diagnostic groups: cognitively healthy persons (ND, n=65), VD (n=56) and Alzheimer disease (AD, n=115) .
The following candidate genes respectively their polymorphisms were investigated:
ApoE;
LRP C766T polymorphism in exon 3;
SREBP-1a deletion-polymorphism in position -36 in the 5'-untranslated region;
PPAR-alpha L162V polymorphism in exon 5;
PPAR-gamma P12A polymorphism in exon 1;
C/T polymorphism on Position –889 in the untranslated region of IL-1;
IL-6 vntr polymorphism in the 3' untranslated region of the IL-6 gene;
Val 125 Leu polymorphism in exon 3, Asn 563 Ser polymorphism in exon 8, and Gly670Arg polymorphism in exon 12 of the PECAM-1 gene;
Ins/Del polymorphism in intron 15 of the ACE gene
Evaluation was done using descriptive statistics and analysis of variance. Ergebnis: The VD group (n=56) was genetically different compared to both groups, patients with Alzheimer disease (AD, n=115) and cognitively healthy persons (ND, n=65). For VD, there was a statistically significant correlation between some genetic markers and wmL load. Schlussfolgerung: Regarding procentual frequency of the polymorphisms genetic pattern in patients with VD are different to ND but not to the AD group. Similarily, the wmL load is higher in VD and AD is similar, and higher then in ND. The results are to be discussed with regard to interferences in genetic processes due to these polymorphisms, which elevate the risk of a cerebrovascular insult resp. the repair capacity of the brain tissue
In general, the results are strong arguments against dichotomy and for the hypothesis of interaction between VD and AD in older age .
Korrespondierender Autor: Kelemen P
ZI, Neuroradiologie, J 5, 68159 Mannheim
E-Mail: peter.kelemen@zi-mannheim.de
Dementia - White matter lesions - Genetics