Evidence for the genetic role of human leukocyte antigens in low frequencyDRBI*1501 multiple sclerosis patients in Israel

A strong association exists between multiple sclerosis (MS) and the DRBI*15 01 haplotype, in most populations. Linkage of Multiple Sclerosis (MS) with the MHC or HLA region on chromosome 6p21 has previously been observed in DR BI*1501 positive MS families. A group of 13 Israeli multiplex MS families w ith a very low frequency of DRBI*1501 haplotype were examined in this study . Association and a linkage test were Performed in order to identify a non- DRBI*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: DRBI, DQAI and DQBI, BAT-2, MIB and D6S248. Data analyses included: (a) an association study comparing the patient gro up with both healthy relative, and healthy control groups (b) a transmissio n test for linkage disequilibrium (TDT) of the MS-associated alleles in the multiplex families, and (c) multipoint non-parametric linkage (NPL) and pa rametric LOD score analyses using the GENEHUNTER program. The DRBI*1303 all ele was significantly more frequent among the MS patients. There was a tren d towards transmission disequilibrium of DRBI*1303, but was not statistical ly significant Allele sharing and LOD score analyses revealed no evidence f or linkage. The high frequency of DRBI*1303 observed in our family patients provides evidence to support the association with this allele that previou sly described in sporadic non-Ashkenazi MS patients. Thus, DRBI*1303 may se rve as genetic risk factor for MS. Our study exemplifies the genetic hetero geneity in MS as there is a genetic effect of HLA on MS susceptibility in o ur low frequency DRBI*1501 patients.