title: CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis. Multiple Sclerosis Genetics Group.
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 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.
authors.affiliation: Department of Neurology, University of California at San Francisco 94143-0435, USA.
authors.forename: L F
authors.initials: LF
authors.lastname: Barcellos
authors.forename: A M
authors.initials: AM
authors.lastname: Schito
authors.forename: J B
authors.initials: JB
authors.lastname: Rimmler
authors.forename: E
authors.initials: E
authors.lastname: Vittinghoff
authors.forename: A
authors.initials: A
authors.lastname: Shih
authors.forename: R
authors.initials: R
authors.lastname: Lincoln
authors.forename: S
authors.initials: S
authors.lastname: Callier
authors.forename: M K
authors.initials: MK
authors.lastname: Elkins
authors.forename: D E
authors.initials: DE
authors.lastname: Goodkin
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: S L
authors.initials: SL
authors.lastname: Hauser
authors.forename: J R
authors.initials: JR
authors.lastname: Oksenberg
mesh_terms: D017668:Age of Onset; D002879:Chromosomes, Human, Pair 10; D002893:Chromosomes, Human, Pair 3; D005260:Female; D006801:Humans; D008126:Lod Score; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*; D012737:Sex Factors; D044465:White People
chemical_list: D019713:Receptors, CCR5