title: 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.
authors.affiliation: Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122, Milan, Italy. daniela.galimberti@unimi.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Diego
authors.initials: D
authors.lastname: Scalabrini
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Milena
authors.initials: M
authors.lastname: De Riz
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Comi
authors.forename: Eliana
authors.initials: E
authors.lastname: Venturelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Cortini
authors.forename: Mirko
authors.initials: M
authors.lastname: Piola
authors.forename: Maurizio
authors.initials: M
authors.lastname: Leone
authors.forename: Umberto
authors.initials: U
authors.lastname: Dianzani
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.forename: Francesco
authors.initials: F
authors.lastname: Monaco
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D054422:Chemokine CCL22 / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008297:Male; D005810:Multigene Family / Q000235:genetics; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012727:Sex Characteristics; D012737:Sex Factors
chemical_list: D054422:Chemokine CCL22; D005819:Genetic Markers