title: Evidence for the genetic role of human leukocyte antigens in low frequency DRB1*1501 multiple sclerosis patients in Israel.
abstract: A strong association exists between multiple sclerosis (MS) and the DRB1*1501 haplotype, in most populations. Linkage of Multiple Sclerosis (MS) with the MHC or HLA region on chromosome 6p21 has previously been observed in DRB1*1501 positive MS families. A group of 13 Israeli multiplex MS families with a very low frequency of DRB1*1501 haplotype were examined in this study. Association and a linkage test were performed in order to identify a non-DRB1*1501 effect of HLA on susceptibility for MS. MS multiplex families and healthy controls were molecularly typed for six highly polymorphic markers located within the MHC region: DRB1, DQA1 and DQB1, BAT-2, MIB and D6S248. Data analyses included: (a) an association study comparing the patient group with both healthy relative, and healthy control groups (b) a transmission test for linkage disequilibrium (TDT) of the MS-associated alleles in the multiplex families, and (c) multipoint non-parametric linkage (NPL) and parametric LOD score analyses using the GENEHUNTER program. The DRB1*1303 allele was significantly more frequent among the MS patients. There was a trend towards transmission disequilibrium of DRB1*1303, but was not statistically significant. Allele sharing and LOD score analyses revealed no evidence for linkage. The high frequency of DRB1*1303 observed in our family patients provides evidence to support the association with this allele that previously described in sporadic non-Ashkenazi MS patients. Thus, DRB1*1303 may serve as genetic risk factor for MS. Our study exemplifies the genetic heterogeneity in MS as there is a genetic effect of HLA on MS susceptibility in our low frequency DRB1*1501 patients.
authors.affiliation: Department of Neurology, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Karni
authors.forename: Y
authors.initials: Y
authors.lastname: Kohn
authors.forename: C
authors.initials: C
authors.lastname: Safirman
authors.forename: O
authors.initials: O
authors.lastname: Abramsky
authors.forename: L
authors.initials: L
authors.lastname: Barcellos
authors.forename: J R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: E
authors.initials: E
authors.lastname: Kahana
authors.forename: D
authors.initials: D
authors.lastname: Karussis
authors.forename: J
authors.initials: J
authors.lastname: Chapman
authors.forename: C
authors.initials: C
authors.lastname: Brautbar
mesh_terms: D000483:Alleles; D005190:Family; D006680:HLA Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D007557:Israel; D015810:Linkage Disequilibrium; D008126:Lod Score; D008499:Medical Records; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology*; D009679:Nuclear Family
chemical_list: D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains