CXCL10 haplotypes and multiple sclerosis: association and correlation with clinical course.
CXCL10 (interferon-gamma-inducible protein-10) levels are increased in cerebrospinal fluid of multiple sclerosis (MS) patients with symptomatic attacks of inflammatory demyelination, supporting a role for this molecule in MS pathogenesis. Two hundred and twenty-six patients with MS and 235 controls were genotyped for G --> C and T --> C single nucleotide polymorphisms (SNPs) in exon 4 of CXCL10 gene. Haplotypes were tested for association and correlated with clinical variables. The two SNPs studied were in complete linkage disequilibrium. None of the determined haplotypes was associated with MS. However, carriers of the GGTT haplotype (defined as wild type, according to the sequence in National Centre for Biotechnology Information (NCBI) database) had a significantly lower progression index than non-carriers (P = 0.016). Furthermore, amongst patients who had an initial relapsing remitting (RR) course of the disease, the time between onset and second episode was significantly longer in GGTT carriers (P = 0.021). Considering secondary progressive (SP)-MS patients, the time between the initial RR form and the subsequent worsening to SP was longer in this group (P = 0.08). Therefore, the GGTT haplotype of the CXCL10 gene is not a susceptibility factor for the development of MS, but is probably to influence the course of MS, possibly contributing to slow down the progression of the disease.
Galimberti
D
D
Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Milan, Italy. daniela.galimberti@unimi.it
Scalabrini
D
D
Fenoglio
C
C
Comi
C
C
De Riz
M
M
Venturelli
E
E
Lovati
C
C
Mariani
C
C
Monaco
F
F
Bresolin
N
N
Scarpini
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics*; D003596:Cytosine; D018450:Disease Progression; D005091:Exons; D005260:Female; D005838:Genotype; D006147:Guanine; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics / Q000503:physiopathology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics / Q000503:physiopathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D013941:Thymine
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D006147:Guanine; D003596:Cytosine; D013941:Thymine