Gender-specific influence of the chromosome 16 chemokine gene cluster on the susceptibility to Multiple Sclerosis.

Abstract Macrophage-derived chemokine (MDC/CCL22) plays a role in Experimental Autoimmune Encephalomyelitis (EAE), the animal model of Multiple Sclerosis (MS). MDC/CCL22 gene is part of a chemokine cluster, which includes also thymus and Activation-Regulated Chemokine (TARC/CCL17). The frequency of the C/T and C/A Single Nucleotide Polymorphisms (SNPs) in the promoter and coding sequence of CCL22 as well as the C/T SNP in the promoter of CCL17 were determined in 370 patients with Multiple Sclerosis (MS) compared with 380 controls. A trend towards a decreased allelic frequency of the A allele of the CCL22 C/A SNP as well as of the T allele of the CCL17 C/T SNP was found in patients compared with controls. The frequency of the AT haplotype was significantly decreased in MS patients ( P  = 0.017, OR: 0.49, CI: 0.28–0.87). Stratifying patients according to gender, the observed association was even more pronounced in male patients compared with male controls ( P  = 0.004, OR = 0.18, 95% CI: 0.06–0.50), whereas no significant differences were observed in females. Therefore, the presence of the AT haplotype in chromosome 16 chemokine cluster is likely to confer a decreased risk of developing MS, particularly in males.