Association study of Parkin gene polymorphisms with idiopathic Parkinson disease

Arch Neurol. 2003 Jul;60(7):975-80. doi: 10.1001/archneur.60.7.975.

Abstract

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Ligases / genetics*
  • Male
  • Middle Aged
  • Parkinson Disease / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics*
  • Ubiquitin-Protein Ligases*

Substances

  • Ubiquitin-Protein Ligases
  • parkin protein
  • Ligases