CCL genes in multiple sclerosis and systemic lupus erythematosus

Abstract

This follow up study aims to refine the roles of previously suggested candidate genes (CC chemokine ligands or CCLs) in multiple sclerosis (MS), and to test these markers in another autoimmune disorder, systemic lupus erythematosus (SLE). After stringent correction for multiple testing, we reject the importance of previously suggested borderline associations with CCLs in MS. A new finding is the differential distribution of CCL8 marker alleles and a haplotype in extreme severity subgroups of MS. In SLE, this study reveals strong associations with a marker and a haplotype encompassing the CCL14 gene, which suggests that a lupus relevant variant may lie within or in the proximity of this haplotype.

Fig. 1

The figure depicts the 17q11.2–q21 region (1.83 MB) with 1,508,243 bp gap between CCL1 and CCL5 and a 96,158 bp gap between CCL5 and CCL16. The lower part of the figure indicates the placing of markers in the phase I (open circles) (Vyshkina et al., 2005), phase II (open stars) (Vyshkina and Kalman, 2005) and present study (diamonds). Upper bars (striped) in the top part of the figure indicate MS-associated haplotypes in the phase I study and lower bars (dotted) indicate MS-associated haplotypes in the phase II study. Note the overlap in markers and haplotypes within the genes of CCL15 and CCL3. The main rational for the selection of the present markers was to include SNPs previously associated with MS, tagging SNPs and non-synonymous mutations in genes of interest.