CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis. Multiple Sclerosis Genetics Group.

Journal Article (Journal Article)

Multiple sclerosis (MS) is a common disease of the central nervous system characterized by myelin loss and progressive neurological dysfunction. An underlying genetic susceptibility plays a clear role in the etiology of MS, likely acting in concert with an undefined environmental exposure. Full-genome screenings in multiplex MS families have identified several susceptibility regions, supporting a polygenic model for MS. Among these regions, evidence for weak linkage was observed at 3p/3cen suggesting the presence of an MS gene(s) of modest effect. Encoded here are two chemokine receptors, CCR5 and CCR2B. We examined the chromosome 3p21-24 region in 125 MS families (322 total affecteds and 200 affected sib-pairs), and performed genetic analyses of CCR5 and CCR2B loci and two nearby markers (D3S1289 and D3S1300) using both linkage- and association-based tests. No evidence of linkage to MS was observed for any of the tested markers. Affected relative-pair (SimIBD) and sib-pair analyses (ASPEX), and association testing (sib-TDT) for each locus were also not significant. However, age of onset was approximately 3 years later in patients carrying the CCR5delta32 deletion (P=0.018 after controlling for gender effects). Thus, chemokine receptor expression may be associated with differential disease onset in a subset of patients, and may provide a therapeutic target to modulate inflammatory demyelination.

Full Text

Duke Authors

Cited Authors

  • Barcellos, LF; Schito, AM; Rimmler, JB; Vittinghoff, E; Shih, A; Lincoln, R; Callier, S; Elkins, MK; Goodkin, DE; Haines, JL; Pericak-Vance, MA; Hauser, SL; Oksenberg, JR

Published Date

  • April 2000

Published In

Volume / Issue

  • 51 / 4-5

Start / End Page

  • 281 - 288

PubMed ID

  • 10803840

International Standard Serial Number (ISSN)

  • 0093-7711

Digital Object Identifier (DOI)

  • 10.1007/s002510050621


  • eng

Conference Location

  • United States