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Association Study of Parkin Gene Polymorphisms With Idiopathic Parkinson Disease
Sofia A. Oliveira, PhD;
William K. Scott, PhD;
Martha A. Nance, MD;
Ray L. Watts, MD;
Jean P. Hubble, MD;
William C. Koller, MD;
Kelly E. Lyons, PhD;
Rajesh Pahwa, MD;
Matthew B. Stern, MD;
Bradley C. Hiner, MD;
Joseph Jankovic, MD;
William G. Ondo, MD;
Fred H. Allen, Jr, MD;
Burton L. Scott, MD;
Christopher G. Goetz, MD;
Gary W. Small, MD;
Frank L. Mastaglia, MD;
Jeffrey M. Stajich, PA-C;
Fengyu Zhang, PhD;
Michael W. Booze, BS;
Joshua A. Reaves, BS;
Lefkos T. Middleton, MD;
Jonathan L. Haines, PhD;
Margaret A. Pericak-Vance, PhD;
Jeffery M. Vance, MD, PhD;
Eden R. Martin, PhD
Arch Neurol. 2003;60:975-980.
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.
From the Department of Medicine and Center for Human Genetics, Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, NC (Drs Oliveira, W. K. Scott, B. L. Scott, Zhang, Pericak-Vance, Vance, and Martin and Messrs Stajich, Booze, and Reaves); Struthers Parkinson Center, Golden Valley, Minn (Dr Nance); Department of Neurology, Emory University School of Medicine, Atlanta, Ga (Dr Watts); Department of Neurology, Ohio State University, Columbus (Dr Hubble); Department of Neurology, University of Miami School of Medicine, Miami, Fla (Drs Koller and Lyons); Department of Neurology, University of Kansas Medical Center, Kansas City (Dr Pahwa); Department of Neurology, University of Pennsylvania Health System, Philadelphia (Dr Stern); Department of Neurology, Marshfield Clinic, Marshfield, Wis (Dr Hiner); Department of Neurology, Baylor College of Medicine, Houston, Tex (Drs Jankovic and Ondo); Carolina Neurologic Clinic, Charlotte, NC (Dr Allen); Department of Neurological Sciences, Rush-Presbyterian-St Luke's Hospital, Chicago, Ill (Dr Goetz); Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles (Dr Small); Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Perth (Dr Mastaglia); GlaxoSmithKline Research and Development, Greenford, Middlesex, England (Dr Middleton); and Program in Human Genetics, Vanderbilt University Medical Center, Nashville, Tenn (Dr Haines).
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