Association of haplotypes in the beta-chemokine locus with multiple sclerosis.
Linkage studies in multiple sclerosis (MS) identified several susceptibility loci. One of these regions includes chromosome 17q11 where a meta-analysis of data from three genome scans suggested linkage. This region encodes a cluster of genes for beta-chemokines or CC chemokine ligands (CCLs), which may be involved in the development of MS lesions. Here we aimed to test if CCL alleles and haplotypes are associated with MS. Using methods of linkage and association, we observed deviations from the expected 50% transmission of haplotypes from unaffected parents to their affected children at CCL2, CCL11-CCL8-CCL13 and CCL3 within the investigated 1.85 MB chromosomal segment. Analyses of the linkage disequilibrium map support that variants with possible relevance to MS can be located within these subregions. Identification of MS associated CCL variants may have direct clinical significance, as it can lead to the design of small competitive antagonists of these molecules with beneficial effects in the treatment of patients with early and active disease.
Vyshkina
Tamara
T
Department of Neurology, SLRHC, Columbia University, 432W 58th Street, New York, NY 10019, USA.
Shugart
Yin Yao
YY
Birnbaum
Gary
G
Leist
Thomas P
TP
Kalman
Bernadette
B
D019742:Chemokines, CC / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*
D019742:Chemokines, CC