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

Department of Neurology, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, Israel

Y Kohn

Department of Psychiatry, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, Israel

C Saftirmnn

Tissue Typing Unit, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, Israel, Lautenberg Cen ter for Gen eral an d Tumor Immun ology, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, Israel

O Abraimsky

Department of Neurology, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, Israel

L Barcellos

Department of Neurology, University of California, San Francisco, California, USA

J R Oksenberg

Department of Neurology, University of California, San Francisco, California, USA

E Kahana

Department of Neurology, Barzilai Medical Center, Ashkelon, Israel

D Karussis

Department of Neurology, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, Israel

J Chapman

Department of Neurology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel-Avi, Israel

C Brautbur

Tissue Typing Unit, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, Israel, Lautenberg Cen ter for Gen eral an d Tumor Immun ology, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, Israel

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.

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

Multiple Sclerosis, Vol. 5, No. 6, 410-415 (1999)
DOI: 10.1177/135245859900500i607


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