title: P-selectin glycoprotein ligand-1 variable number of tandem repeats (VNTR) polymorphism in patients with multiple sclerosis.
abstract: P-selectin glycoprotein ligand-1 (PSGL-1) is an important adhesion molecule involved in lymphocyte recruitment into the brain, which represents a crucial step in the pathogenesis of multiple sclerosis (MS). Three hundred twenty-one MS patients and 342 controls were genotyped for the presence of a polymorphism in the PSGL-1 gene, consisting of a variable number of tandem repeats (VNTR) originating three possible alleles: A, B and C, in order to test whether they influence the susceptibility and the course of the disease. No significant differences among allelic frequencies of A, B and C alleles in MS as compared with controls were observed. Stratifying patients according to the course of the disease, a significantly increased frequency of the shortest C allele in PP-MS was found (7.1%), either in comparison with controls (P=0.011) or with all other MS patients, who had acute inflammatory attacks at onset and an initial RR form (P=0.036). Besides, none of SP-MS patients was a carrier of the C allele and B carriers converted later from RR to SP course as compared with A/A subjects (after 15.8 rather than 8.8 years, P=0.01). In conclusion, the C allele of the VNTR polymorphism in PSGL-1 is likely to be associated with PP-MS. As this allele has been demonstrated to have a very low efficiency in mediating lymphocyte binding to brain endothelium during attacks, its high frequency in PP-MS could be related to the absence of exacerbations in such patients.
authors.affiliation: Department of Neurological Sciences, "Dino Ferrari" Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122 Milan, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Scalabrini
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Cristoforo
authors.initials: C
authors.lastname: Comi
authors.forename: Milena
authors.initials: M
authors.lastname: De Riz
authors.forename: Eliana
authors.initials: E
authors.lastname: Venturelli
authors.forename: Luca
authors.initials: L
authors.lastname: Castelli
authors.forename: Laura
authors.initials: L
authors.lastname: Piccio
authors.forename: Marco
authors.initials: M
authors.lastname: Ronzoni
authors.forename: Carlo
authors.initials: C
authors.lastname: Lovati
authors.forename: Claudio
authors.initials: C
authors.lastname: Mariani
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; D017668:Age of Onset; D002448:Cell Adhesion / Q000235:genetics; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D018598:Minisatellite Repeats / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein