CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis

Lisa F. Barcellos, Anna M. Schito, Jackie B. Rimmler, Eric Vittinghoff, Andrew Shih, Robin Lincoln, Stacy Callier, Mary K. Elkins, Donald E. Goodkin, Jonathan L. Haines, Margaret A Pericak-Vance, Stephen L. Hauser, Jorge R. Oksenberg

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

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 CCR5Δ32 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.

Original languageEnglish
Pages (from-to)281-288
Number of pages8
JournalImmunogenetics
Volume51
Issue number4-5
StatePublished - Apr 22 2000
Externally publishedYes

Fingerprint

CCR5 Receptors
Age of Onset
Multiple Sclerosis
Chemokine Receptors
Central Nervous System Diseases
Environmental Exposure
Demyelinating Diseases
Genetic Predisposition to Disease
Myelin Sheath
Chromosomes
Genome

Keywords

  • Autoimmunity
  • Chemokine
  • Human
  • Major histocompatibility complex
  • Multiple sclerosis

ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this

Barcellos, L. F., Schito, A. M., Rimmler, J. B., Vittinghoff, E., Shih, A., Lincoln, R., ... Oksenberg, J. R. (2000). CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis. Immunogenetics, 51(4-5), 281-288.

CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis. / Barcellos, Lisa F.; Schito, Anna M.; Rimmler, Jackie B.; Vittinghoff, Eric; Shih, Andrew; Lincoln, Robin; Callier, Stacy; Elkins, Mary K.; Goodkin, Donald E.; Haines, Jonathan L.; Pericak-Vance, Margaret A; Hauser, Stephen L.; Oksenberg, Jorge R.

In: Immunogenetics, Vol. 51, No. 4-5, 22.04.2000, p. 281-288.

Research output: Contribution to journalArticle

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 2000, 'CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis', Immunogenetics, vol. 51, no. 4-5, pp. 281-288.
Barcellos LF, Schito AM, Rimmler JB, Vittinghoff E, Shih A, Lincoln R et al. CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis. Immunogenetics. 2000 Apr 22;51(4-5):281-288.
Barcellos, Lisa F. ; Schito, Anna M. ; Rimmler, Jackie B. ; Vittinghoff, Eric ; Shih, Andrew ; Lincoln, Robin ; Callier, Stacy ; Elkins, Mary K. ; Goodkin, Donald E. ; Haines, Jonathan L. ; Pericak-Vance, Margaret A ; Hauser, Stephen L. ; Oksenberg, Jorge R. / CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis. In: Immunogenetics. 2000 ; Vol. 51, No. 4-5. pp. 281-288.
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