ALCAM--novel multiple sclerosis locus interfering with HLA-DRB1*1501.

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-DRB11501 effect. Results obtained from logistic regression analysis showed five-fold lower risk for MS for both rs11559013GA/HLA-DRB11501+ and rs34926152GT/HLA-DRB11501+ individuals. This observations may suggest protective role against MS for both rs11559013GA and rs34926152GT genotypes in HLA-DRB11501 positive individuals.