TY - JOUR
T1 - P-selectin glycoprotein ligand-1 variable number of tandem repeats (VNTR) polymorphism in patients with multiple sclerosis
AU - Scalabrini, Diego
AU - Galimberti, Daniela
AU - Fenoglio, Chiara
AU - Comi, Cristoforo
AU - De Riz, Milena
AU - Venturelli, Eliana
AU - Castelli, Luca
AU - Piccio, Laura
AU - Ronzoni, Marco
AU - Lovati, Carlo
AU - Mariani, Claudio
AU - Monaco, Francesco
AU - Bresolin, Nereo
AU - Scarpini, Elio
N1 - Funding Information:
This work was supported by grants from Associazione “Amici del Centro Dino Ferrari”, IRCCS Ospedale Maggiore Milano, Centre of Excellence for Neurodegenerative Diseases of the University of Milan and Ing. Cesare Cusan.
PY - 2005/11/18
Y1 - 2005/11/18
N2 - 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.
AB - 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.
KW - Adhesion molecules
KW - Genetics
KW - Multiple sclerosis
KW - P-selectin glycoprotein ligand-1
KW - Polymorphism
UR - http://www.scopus.com/inward/record.url?scp=23944484234&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2005.06.059
DO - 10.1016/j.neulet.2005.06.059
M3 - Article
C2 - 16039046
AN - SCOPUS:23944484234
SN - 0304-3940
VL - 388
SP - 149
EP - 152
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 3
ER -