#15-OR
THE INFLUENCE OF HLA-C ALLELES ON MULTIPLE SCLEROSIS IN AFRICAN AMERICANS.
B. Hoglund BS , T. L. Bugawan, BS , L. Barcellos PhD , J. Oksenberg PhD , W. Klitz PhD and H. A. Erlich, PhD . Oakland CA, USA, Children
s Hospital Oakland Research Institute, Research ; Alameda CA, USA, Roche Molecular Systems, Human Genetics ; San Francisco CA, USA, UC San Francisco, Dept. of Neurology and Berkeley CA, USA, Univ. of California, School of Public Health .
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system white matter characterized by inflammation, demyelination and progressive axonal injury. An underlying complex genetic susceptibility exists in MS, and an association with the HLA-DRB1*1501-DQB1*0602 haplotype has been repeatedly demonstrated in high-risk populations. To date, little is known about the HLA class I association with MS. Here, we report the first HLA-C association with MS in an African American population. A total of 320 MS probands, 190 mothers, 78 fathers and 64 spouses of probands were genotyped. A total of 33 distinct HLA C alleles were identified. The frequency distributions of the patient and control samples were compared with the loglikelihood ratio statistic, which gave a value of 24.0 with 16 degrees of freedom, and a resulting P value of 0.090. Interestingly, the C*0802 allele is much less frequent than expected in the patient sample (OR=0.43, P=0.0037). In order to determine the relationship of this apparently protective factor to the MS predispositional factor DRB1*15, we constructed a table of the presence and absence in individuals of C*0802 and DRB1*15 divided according to disease status (patients/controls). The overall 2 by 4 test reveals that the two-locus genotypes do indeed impact disease outcome (P=0.0014). Both HLA-C and DRB1 are influential, but in different directions. Carriage of C*0802 seems to confer protection, regardless of DRB1*15, while the DRB1*1501 predispositional effect is seen only in the absence of C*0802. A six-fold difference in MS risk is present between individuals carrying C*0802 and those carrying a DRB1*15 allele without C*0802 (P<0.00002).