CYP2D6 gene polymorphism as a probable risk factor for Alzheimer's disease and Parkinson's disease with dementia.
OBJECTIVE
The theory of multifactorial inheritance is considered in the pathogenesis of sporadic Alzheimer's disease (AD) and Parkinson's disease (PD); therefore, it makes the genes regulating bioactivation or detoxification of exogenous substances candidates of sensitivity to Alzheimer's and Parkinson's diseases. The aims of the study were: 1) to determine the genotypes of CYP2D6 cytochrome (CYP2D6) in patients with AD and sporadic PD with dementia; 2) to evaluate the relationship between the CYP2D6 genotype and the age of onset of the disease, the extent of dementia in AD and PD, the dose and side effects of L-dopa in PD; 3) to evaluate the usefulness of CYP2D6 genotyping in predicting predispositions to PD and AD.


METHODS
53 patients with AD aged 58-84 (mean age 72.6) and 52 patients with PD with dementia aged 51-82 (mean age 70.4) were recruited. Each AD patient satisfied criteria for probable AD. Diagnostic and Statistical Manual of Mental Disorders 4th edition, Mini-Mental State Examination, Clinical Dementia Rating Scale and Global Deterioration Scale were used for dementia evaluation in PD patients. Clinical scales for PD evaluation were used. Methods of molecular biology were used for genetic studies.


RESULTS
There were no differences in CYP2D6 genotype and allele distribution in AD and PD patients. There was no relationship between CYP2D6 alleles and the age of onset and advancement of dementia in AD and PD. No relationship between CYP2D6 alleles and the dose and side effects of L-dopa in patients with sporadic PD with dementia was observed.


CONCLUSIONS
As there were no differences in CYP2D6 polymorphism in AD and PD, CYP2D6 does not seem to be a factor predisposing to these diseases.
Gołab-Janowska
Monika
M
Katedra i Klinika Neurologii, Pomorskiej Akademia Medyczna, Szczecin. glissanda1@poczta.onet.pl
Honczarenko
Krystyna
K
Gawrońska-Szklarz
Barbara
B
Potemkowski
Andrzej
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D000978:Antiparkinson Agents / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003704:Dementia / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012720:Severity of Illness Index
D000978:Antiparkinson Agents; D007980:Levodopa; D019389:Cytochrome P-450 CYP2D6