ISSN 10227954, Russian Journal of Genetics, 2010, Vol. 46, No. 3, pp. 265–275. © Pleiades Publishing, Inc., 2010.
Original Russian Text © O.O. Favorova, O.G. Kulakova, A.N. Boiko, 2010, published in Genetika, 2010, Vol. 46, No. 3, pp. 302–313.
Multiple sclerosis (MS) is a chronic inflammatory
disease of central nervous system resulting in disability.
At present MS is detected in nearly each world popu
lation, but more frequently in northern regions .
According to the data of 2007, 380000 MS patients
resided in 28 European countries; for their treatment
and maintenance 12.5 billion Euros has been spent
annually . MS is one of the most socially essential
neurological problems because the majority of MS
patients are young people, who are socially and profes
sionally active .
The early data on potential genetic predisposition
to MS were obtained from epidemiologic studies,
which revealed different incidence of MS in various
ethnic groups residing on the same territory. MS is
more frequently observed in the families with MS
patients than in the whole population . However,
the disease transmission within the family is not Men
delian . The recurrence risk of MS for relatives of
MS patients is 20–50 times higher than on average in
the population , and a systematic decrease in this
value depending on the relative genetic distance to the
proband is also observed [7, 8]. Such mode of inherit
ance is characteristic for polygenic diseases, which
arise from the combined contributions of multiple
independent or interacting polymorphic genes .
The studies on MS etiology have led to a suggestion
that both hereditary predisposition and environmental
factors are required for the disease development. The
number of hypothetic mechanisms has been sug
gested, according to which infectious agents (such as
viruses and bacteria) and other environmental factors
could affect the risk of MS development. Although
family studies in the individual groups (sibs, halfsibs,
adopted children, spouses, etc.) showed that environ
mental factors are less important than genetics at the
family level [10, 11], it is commonly accepted at
present that MS, like the majority of other common
diseases, depends on genetic component and environ
mental factors, which are in programmed or random
interaction with each other . The complexity of
these interactions does not permit to predict MS
development unequivocally basing on a single trait.
However, even identification of the limited contribu
tion of any individual gene in MS development or pro
gression can facilitate the understanding of the biolog
ical nature of the disease and reveal new possibilities
for its prevention or treatment.
SEARCH FOR GENES RESPONSIBLE
FOR MS DEVELOPMENT
Since recently the search for genes responsible for
MS development has been conducted using two main
approaches: (1) analysis of association of the individ
ual “candidate genes” with the disease and (2) analysis
of linkage with the disease of the wide spectrum of
chromosomal loci (whole genome search) in the fam
ilies with several MS patients. In case of whole genome
screen, panels of anonymous genetic markers of
known chromosome localization and more or less uni
form distribution in the genome were used. Based on
these data, one can localize genome regions that are
involved in the disease development and then search
for genes linked to this disease in these regions. This
approach could be determined as a pathway “from the
Multiple Sclerosis as a Polygenic Disease: An Update
O. O. Favorova, O. G. Kulakova, and A. N. Boiko
Russian State Medical University, Moscow 117997 Russia;
Received March 2, 2009
—Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The
observed type of heredity associated with MS is characteristic of polygenic diseases, which arises from a joint
contribution of a number of independently acting or interacting polymorphic genes. Recently to identify the
genes responsible for genetic predisposition to MS two main approaches have been applied: (1) analysis of
association of individual “candidate genes” with the disease and (2) analysis of the wide spectrum of chro
mosomal loci (whole genome screen) linkage with the disease in families with several MS patients. In the last
two years, a new method, which borrowed the best approaches of the previous studies, genomewide associ
ation screening (GWAS), which is based on the modern highthroughput DNA analysis, has been developed.
This review describes replicated (validated) results for individual genes and DNA loci located on the majority
of chromosomes obtained using these three strategies as well as data on association of MS with allelic combi
nations of various genes.
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