Abstract
Multiple sclerosis (MS) is a complex disease; at an intra-individual
level several contributory factors cause the disease; at an
inter-individual level different factors contribute to the disease. The
aim of the thesis project was to reduce this complexity by focusing of
subsets of patients that were likely to share to a higher extent
contributory causes and to identify in these subsets genes conferring
susceptibility.
In paper I we wanted to know the HLA-DRB1 allele associated to the small
fraction of MS patients lacking signs of immunoglobulin synthesis within
the central nervous system (OCB-negative MS). In papers III and IV we
performed whole-genome singlenucleotide-polymorphism (SNP) scans to
identify genetic susceptibility regions in distantly related patients
from an MS cluster in a parish in Värmland (paper III) and in a
consanguineous family with several affected family members (paper IV). We
also asked the question if differences in etiology are reflected in
clinical parameters such as the severity of the disease, which we looked
at in both papers I and II in relation to OCB status (I and II) and
HLA-DRB1 alleles (II).
Some of the main results in this thesis project and their congruence with
previous reports of genetic susceptibility in MS are the following: the
association between the OCB-negative entity and HLA-DRB1*04 seen both in
our population and in Japan; the potential importance of the ACCN1 gene,
identified in our distantly related MS patients and in an isolated
population in Sardinia; the role of mutations in the PLP1 gene on the X
chromosome reported in two MS case reports, thus indicating the
plausibility of monogenic X-linked MS.
The results derived from this thesis project merit follow-up.
