Association of haplotypes in the -chemokine locus with multiple sclerosis

• Published in: European journal of human genetics : EJHG Vol. 13; no. 2; pp. 240 - 247
• Main Authors: Vyshkina, Tamara, Yin Yao Shugart, Birnbaum, Gary, Leist, Thomas P, Kalman, Bernadette
• Format: Journal Article
• Language: English
• Published: Leiden Nature Publishing Group 01.02.2005
• Subjects: Alleles; Antagonists; CCL3 protein; Cell cycle; Chemokines; Children; Chromosome 17; Data processing; Deoxyribonucleic acid; Disease; DNA; Epidemiology; Genes; Genetics; Genomes; Haplotypes; Ligands; Linkage disequilibrium; Monocyte chemoattractant protein 1; Multiple sclerosis; Neurology; Patients; Sclerosis; New York; United States > US; San Francisco California
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/sj.ejhg.5201295

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.