Gender-specific influence of the chromosome 16 chemokine gene cluster on the susceptibility to Multiple Sclerosis.
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.
Galimberti
Daniela
D
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
Scalabrini
Diego
D
Fenoglio
Chiara
C
De Riz
Milena
M
Comi
Cristoforo
C
Venturelli
Eliana
E
Cortini
Francesca
F
Piola
Mirko
M
Leone
Maurizio
M
Dianzani
Umberto
U
D'Alfonso
Sandra
S
Monaco
Francesco
F
Bresolin
Nereo
N
Scarpini
Elio
E
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
D054422:Chemokine CCL22; D005819:Genetic Markers