A study of five candidate genes in Parkinson's disease and related neurodegenerative disorders. European Study Group on Atypical Parkinsonism.
OBJECTIVE
To determine whether reported genetic association of polymorphisms in the CYP2D6, CYP1A1, N-acetyltransferase 2 (NAT2), DAT1, and glutathione s-transferase M1 (GSTM1) genes with PD were evident in a population of 176 unrelated patients with sporadic PD and to extend these findings to other disease groups (familial PD [n = 30], ALS [n = 50], multiple system atrophy [n = 38], progressive supranuclear palsy [n = 35], and AD [n = 23]).


METHODS
A combination of allele-specific PCR and analysis of restriction fragment length polymorphisms were performed.


RESULTS
We genotyped 1,131 individuals. After matching each patient with a control subject by age, sex, ethnicity, and geographic origin, there was no association of any allele/genotype with any of the six disease groups. There was an increased frequency of NAT2 slow acetylators in the ALS group compared with controls (70% versus 50%; OR 2.33 [95% CI, 1.03 to 5.30]), but this was not significant after adjusting for multiple testing.


CONCLUSIONS
This is one of the most extensive candidate gene studies performed in PD and the first time that some of these loci have been studied in multiple system atrophy and progressive supranuclear palsy. In contrast with previous studies, we found no role for these polymorphisms in the etiology of PD, ALS, multiple system atrophy, progressive supranuclear palsy, or AD.
Nicholl
D J
DJ
Department of Clinical Neurology, Queen Elizabeth Hospital & Birmingham University, UK. d.j.nicholl@bham.ac.uk
Bennett
P
P
Hiller
L
L
Bonifati
V
V
Vanacore
N
N
Fabbrini
G
G
Marconi
R
R
Colosimo
C
C
Lamberti
P
P
Stocchi
F
F
Bonuccelli
U
U
Vieregge
P
P
Ramsden
D B
DB
Meco
G
G
Williams
A C
AC
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D013494:Supranuclear Palsy, Progressive / Q000235:genetics