Novel haplotypes in 17q21 are associated with progressive supranuclear palsy

Ann Neurol. 2004 Aug;56(2):249-58. doi: 10.1002/ana.20178.


Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are sporadic neurodegenerative diseases presenting as atypical parkinsonian disorders, characterized by the presence of tau-positive neurofibrillary tangles. Recently, an extended haplotype (H1E) of 787.6 kb that comprises several genes including MAPT showed increased association with PSP. The objective of this study was to determine the size of the H1E haplotype associated with PSP and CBD in different populations and to identify specific subhaplotypes in the background of H1E haplotype. Nineteen single nucleotide polymorphisms (SNPs) in the 17q21 region were genotyped in two case-control samples. The SNPs that were associated with higher risk for the disease in the homozygous state delimit a region of more that 1 Mb. Haplotype analyses in the Spanish sample showed that the most frequent haplotype found among the patients (H1E'), which extends 1.04 Mb and contains several genes such as MAPT, CRHR1, IMP5, Saitohin, WTN3, and NSF. A specific subhaplotype (H1E'A) was present in 16% of PSP patients but was not observed in the controls. Furthermore, the H2E'A haplotype, was rarely present in the disease group suggesting that it plays a protective role. The identification of these specific subhaplotypes that modify risk for PSP/CBD supports the hypothesis that a pathogenic allele exists in a subgroup of PSP patients.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Basal Ganglia
  • Case-Control Studies
  • Cerebral Cortex
  • Chromosomes, Human, Pair 17*
  • Demography
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Haplotypes*
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / genetics*
  • Polymorphism, Single Nucleotide
  • Risk
  • Spain / ethnology
  • Supranuclear Palsy, Progressive / epidemiology
  • Supranuclear Palsy, Progressive / genetics*
  • White People
  • tau Proteins / genetics*


  • tau Proteins