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

Abstract

A strong association exist between m ultiple sclerosis (MS) and the DRB1 *1SO 1 haplotype, in most populations. Linkage of Multiple Sclerosis (MS) with the MHC or HLA region on chromosome 6p2I has previously been observed in DRBI*1SO positive MS families. A group of 13 Israeli multiplex MS families with a very low frequency of DRB 1*1SO1 haplotype were examined in this study. Association and a linkage test were performed in order to identify a non-DRB1*1SO 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: DRBS, DQAI and DQBI, BAT-2, MIB and D65248. Dta 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 DRBI * 1303 allele was significandy more frequent among the MS patiens There was a trend towards transmission disequilibrium of DRBS *1303, but was not statistically significant. Allele sharing and LOD score analyses revealed no evidence for linkage. The high frequency of DRBI * 1303 observed in our family patient provides evidence to support the association with this allele that previously described in sporadic non-Ashkenazi MS patiens Th us, DRBI * 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 DRBS*1SO0 patient.

Keywords

human leukocyte antigens (HLA)major histocompatibility complex (MHC)Multiple Sclerosis (MS)linkage analysis association study GENEHUNTER

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