Association of CCR5 delta32 deletion with early death in multiple sclerosis

Genet Med. 2004 May-Jun;6(3):126-31. doi: 10.1097/01.gim.0000127274.45301.54.

Abstract

Purpose: The interaction between chemokines and their receptors is extremely important in controlling T cell migration into sites of CNS inflammation. Because trafficking of inflammatory T cells into the central nervous system (CNS) is a key player in the pathogenesis of multiple sclerosis (MS), we investigated the possible association of CCR5 delta32 deletion in this disorder.

Methods: DNA isolated from postmortem brain tissue samples of 132 patients with MS and from blood tissue samples of 163 gender and ethnicity-matched healthy controls was used to screen for the CCR5 delta32 deletion allele.

Results: An increased frequency of 32-bp deletion allele was found to be associated with early death (P = 0.00005) and with a progressive reduction in the years of survival (onset to death). The death hazard ratio of CCR5 with deletion versus no deletion was 2.12, suggesting that MS patients with the 32-bp deletion have twice the mortality rate of patients with the normal genotype. This effect was more significant in females (hazard ratio 3.58).

Conclusion: A strong association of the CCR5delta32 deletion with early death could serve as a prognostic marker for MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Case-Control Studies
  • Central Nervous System / immunology
  • Central Nervous System / pathology
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / mortality*
  • Multiple Sclerosis / pathology
  • Predictive Value of Tests
  • Prognosis
  • Receptors, CCR5 / genetics*
  • Sequence Deletion / genetics*
  • Survival Rate
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology

Substances

  • Receptors, CCR5