A functional polymorphism regulating dopamine beta-hydroxylase influences against Parkinson's disease.
A functional --1021C --> T polymorphism in the dopamine beta-hydroxylase gene has been demonstrated to regulate plasma DBH activity. We report that individuals with genetically determined low serum DBH activity (genotype T/T) have protection against Parkinson's disease (p = 0.01). In particular, we observed an underrepresentation of the T/T genotype odds ratio = 0.46 (CI = 0.27-0.8). Rather than identifying a haplotype, or a marker in linkage disequilibrium with the risk variant, this to our knowledge is the first report directly linking PD susceptibility with a proven functional variant.
Healy
Daniel G
DG
Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom.
Abou-Sleiman
Patrick M
PM
Ozawa
Tetsutaro
T
Lees
Andrew J
AJ
Bhatia
Kailash
K
Ahmadi
Kourosh R
KR
Wullner
Ullrich
U
Berciano
Jose
J
Moller
J Carsten
JC
Kamm
Christoph
C
Burk
Katrin
K
Barone
Paolo
P
Tolosa
Eduardo
E
Quinn
Niall
N
Goldstein
David B
DB
Wood
Nicholas W
NW
Barrone
Paolo
P
D000818:Animals; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015331:Cohort Studies; D004299:Dopamine beta-Hydroxylase / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000235:genetics; D016017:Odds Ratio; D002679:Pan troglodytes; D010300:Parkinson Disease / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000502:physiology*; D013912:Threonine / Q000235:genetics
D013912:Threonine; D004299:Dopamine beta-Hydroxylase