title: ALCAM--novel multiple sclerosis locus interfering with HLA-DRB1*1501.
abstract: Activated leukocyte cell adhesion molecule (ALCAM) is a molecule involved in leukocyte migration across the blood-brain barrier which is a key stage in multiple sclerosis (MS) pathogenesis. The present study is the first to report evidence of the association of rs6437585 ALCAM polymorphism with risk and progression of MS. Our investigation revealed that rs6437585CT individuals had higher risk of MS (OR=2.34; 95%CI=1.22-4.51; P=0.011) and over 2 years earlier age of onset (95%CI=0.16-4.41, P=0.036). Moreover, we demonstrated that two ALCAM polymorphisms, rs11559013 and rs34926152, although not associated with MS itself, modify HLA-DRB1*1501 effect. Results obtained from logistic regression analysis showed five-fold lower risk for MS for both rs11559013GA/HLA-DRB1*1501+ and rs34926152GT/HLA-DRB1*1501+ individuals. This observations may suggest protective role against MS for both rs11559013GA and rs34926152GT genotypes in HLA-DRB1*1501 positive individuals.
authors.affiliation: Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. marta_wagner@o2.pl
authors.forename: Marta
authors.initials: M
authors.lastname: Wagner
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wiśniewski
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Bilińska
authors.forename: Anna
authors.initials: A
authors.lastname: Pokryszko-Dragan
authors.forename: Izabela
authors.initials: I
authors.lastname: Nowak
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuśnierczyk
authors.forename: Monika
authors.initials: M
authors.lastname: Jasek
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002648:Child; D005260:Female; D005326:Fetal Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D059811:HLA-DRB1 Chains; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C489631:HLA-DRB1*15:01 antigen