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- Title
CC-chemokine receptor 5 polymorphism and age of onset in familial multiple sclerosis.
- Authors
Barcellos, L. F.; Schito, A. M.; Rimmler, J. B.; Vittinghoff, E.; Shih, A.; Lincoln, R.; Callier, S.; Elkins, M. K.; Goodkin, D. E.; Haines, J. L.; Pericak-Vance, M. A.; Hauser, S. L.; Oksenberg, J. R.
- 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.
- Subjects
MULTIPLE sclerosis; VIRUS diseases; ETIOLOGY of diseases; DISEASE susceptibility; CHEMOKINES; GENETIC polymorphisms; GENETIC testing
- Publication
Immunogenetics, 2000, Vol 51, Issue 4/5, p281
- ISSN
0093-7711
- Publication type
Article
- DOI
10.1007/s002510050621