A haplotype at the PARK3 locus influences onset age for Parkinson's disease: the GenePD study.
OBJECTIVE
To identify a haplotype influencing onset age for Parkinson's disease (PD) in the PARK3 region on chromosome 2p13.


METHODS
Single nucleotide polymorphisms (SNP) spanning 2.2 Mb and located in or near potential candidate genes were used to fine map the PARK3 region in 527 patients with familial PD, from 264 families.


RESULTS
TT homozygotes for rs1876487 (G/T) had a 7.4-year younger mean age at onset (p = 0.005) compared to patients with GT and GG genotypes. Furthermore, SNP flanking the sepiapterin reductase (7,8-dihydrobiopterin: NADP+ oxidoreductase) (SPR) gene, rs1876487 (p = 0.02) and rs1150500 (p = 0.04), were associated with younger onset age among persons who did not carry the 174 allele of D2S1394. The SPR gene is implicated in dopamine synthesis. Haplotype analysis of three SNP-rs2421095, rs1876487, rs1561244-revealed an association with onset age (p = 0.023) and a haplotype of A-T-G alleles was associated with younger onset for PD (p = 0.005).


CONCLUSIONS
A haplotype at the PARK3 locus, harboring the SPR gene, is associated with onset age of PD. This may suggest a role for the SPR gene in modifying the age at onset of PD.
Karamohamed
S
S
Department of Neurology, Boston University School of Medicine, MA 02118, USA. samer@bu.edu
DeStefano
A L
AL
Wilk
J B
JB
Shoemaker
C M
CM
Golbe
L I
LI
Mark
M H
MH
Lazzarini
A M
AM
Suchowersky
O
O
Labelle
N
N
Guttman
M
M
Currie
L J
LJ
Wooten
G F
GF
Stacy
M
M
Saint-Hilaire
M
M
Feldman
R G
RG
Sullivan
K M
KM
Xu
G
G
Watts
R
R
Growdon
J
J
Lew
M
M
Waters
C
C
Vieregge
P
P
Pramstaller
P P
PP
Klein
C
C
Racette
B A
BA
Perlmutter
J S
JS
Parsian
A
A
Singer
C
C
Montgomery
E
E
Baker
K
K
Gusella
J F
JF
Fink
S J
SJ
Myers
R H
RH
Herbert
A
A
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000429:Alcohol Oxidoreductases / Q000235:genetics; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase