title: The killer immunoglobulin-like receptor KIR3DL1 in combination with HLA-Bw4 is protective against multiple sclerosis in African Americans.
abstract: We investigated the role of the KIR loci and their HLA class I ligands in a large cohort of African American multiple sclerosis (MS) patients (N=907) and controls (N=1456). No significant differences in carrier frequencies for any KIR locus or haplotype were observed between cases and controls. However, examination of KIR in the context of their cognate HLA ligands revealed a strong protective effect for KIR3DL1 in combination with HLA-A and -B alleles bearing the Bw4 motif (P=10(-8); odds ratio (OR)=0.60, confidence interval (CI)=0.50-0.71) and the Bw4 ligand alone (P<10(-6); OR=0.63, CI=0.53-0.75). The observed effect cannot be explained by either a specific HLA-B allele or by linkage disequilibrium with HLA-DRB1 or HLA-A. The protective effect was observed only in individuals who were not positive for the MS risk allele HLA-DRB1*15:01 (P<10(-6); OR=0.61, CI=0.51-0.74). Our study, the first investigation of KIR and MS in African Americans, confirms and refines previous findings in a European cohort.
authors: Department of Neurology, University of California, San Francisco, CA, USA.
authors: J A
authors: JA
authors: Hollenbach
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic in Arizona, AZ, USA.
authors: M J
authors: MJ
authors: Pando
authors: Department of Neurology, University of California, San Francisco, CA, USA.
authors: S J
authors: SJ
authors: Caillier
authors: Department of Neurology, University of California, San Francisco, CA, USA.|ATIP-Avenir Inserm Unit 1064, Hospital and University of Nantes, Nantes, France.
authors: P-A
authors: PA
authors: Gourraud
authors: Department of Neurology, University of California, San Francisco, CA, USA.
authors: J R
authors: JR
authors: Oksenberg
mesh_terms: D001741:Black or African American; D000483:Alleles; D016022:Case-Control Studies; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D009103:Multiple Sclerosis / Q000208:ethnology / Q000235:genetics*; D054341:Receptors, KIR3DL1 / Q000235:genetics*
chemical_list: D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1