Association study of Parkin gene polymorphisms with idiopathic Parkinson disease.
BACKGROUND
Previously, we detected linkage of idiopathic Parkinson disease (PD) to the region on chromosome 6 that contains the Parkin gene (D6S305; logarithm of odds score, 5.47) in families with at least one individual with age at onset younger than 40 years (families with early-onset disease). Further study demonstrated the presence of Parkin mutations in this data set. However, previous case-control studies have reported conflicting results regarding the role of more common Parkin polymorphisms as susceptibility alleles for idiopathic PD.


OBJECTIVE
To investigate the association of 7 previously studied Parkin single-nucleotide polymorphisms (SNPs) throughout the promoter and most of the open reading frame with PD in a large cohort of patients with primarily late-onset PD.


METHODS
One promoter, 3 intronic, and 3 exonic Parkin SNPs were genotyped in 1580 individuals belonging to 397 families, and their association with PD was evaluated using family-based association tests.


RESULTS
No significant association (P>.05) between PD and any Parkin SNP allele or genotype was detected. Haplotype analysis and stratification by age at onset or family history also failed to produce significant results.


CONCLUSIONS
These results suggest that these common variants of Parkin are not associated with PD in white patients, although Parkin mutations are known to cause early- and late-onset PD.
Oliveira
Sofia A
SA
Department of Medicine and Center for Human Genetics, Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, NC.
Scott
William K
WK
Nance
Martha A
MA
Watts
Ray L
RL
Hubble
Jean P
JP
Koller
William C
WC
Lyons
Kelly E
KE
Pahwa
Rajesh
R
Stern
Matthew B
MB
Hiner
Bradley C
BC
Jankovic
Joseph
J
Ondo
William G
WG
Allen
Fred H
FH
Scott
Burton L
BL
Goetz
Christopher G
CG
Small
Gary W
GW
Mastaglia
Frank L
FL
Stajich
Jeffrey M
JM
Zhang
Fengyu
F
Booze
Michael W
MW
Reaves
Joshua A
JA
Middleton
Lefkos T
LT
Haines
Jonathan L
JL
Pericak-Vance
Margaret A
MA
Vance
Jeffery M
JM
Martin
Eden R
ER
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases