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.
P-selectin glycoprotein ligand-1 variable number of tandem repeats (VNTR) polymorphism in patients with multiple sclerosis / D. Scalabrini, D. Galimberti, C. Fenoglio, C. Comi, M. De Riz, E. Venturelli, L. Castelli, L. Piccio, M. Ronzoni, C. Lovati, C. Mariani, F. Monaco, N. Bresolin, E.A. Scarpini. - In: NEUROSCIENCE LETTERS. - ISSN 0304-3940. - 388:3(2005), pp. 149-152. [10.1016/j.neulet.2005.06.059]
P-selectin glycoprotein ligand-1 variable number of tandem repeats (VNTR) polymorphism in patients with multiple sclerosis
D. Scalabrini;D. GalimbertiSecondo
;C. Fenoglio;M. De Riz;E. Venturelli;L. Piccio;M. Ronzoni;C. Lovati;C. Mariani;N. BresolinPenultimo
;E.A. Scarpini
2005
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.File | Dimensione | Formato | |
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