CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis. Multiple Sclerosis Genetics Group.
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.
Barcellos
L F
LF
Department of Neurology, University of California at San Francisco 94143-0435, USA.
Schito
A M
AM
Rimmler
J B
JB
Vittinghoff
E
E
Shih
A
A
Lincoln
R
R
Callier
S
S
Elkins
M K
MK
Goodkin
D E
DE
Haines
J L
JL
Pericak-Vance
M A
MA
Hauser
S L
SL
Oksenberg
J R
JR
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
D019713:Receptors, CCR5