1022-7954/02/3802- $27.00 © 2002
Russian Journal of Genetics, Vol. 38, No. 2, 2002, pp. 196–200. Translated from Genetika, Vol. 38, No. 2, 2002, pp. 259–263.
Original Russian Text Copyright © 2002 by Zorkoltseva, Lubinsky, Sharipov, Zaidman, Axenovich, Dimshits.
Idiopathic scoliosis (IS) is a lateral curvature of the
spine, which is the most common type of orthopedic
pathology. Epidemiological studies of Siberian popula-
tions showed that the total frequency of IS reached
17%, and the frequency of pronounced forms (degrees
II to IV) was 1.5–2% . Though IS belongs to the dis-
eases with established hereditary determination
(OMIM No 181800), its etiology remains unclear. Our
previous analysis of a large sample of the patients and
their relatives showed that the inheritance of the pro-
nounced disease forms can be described by an autoso-
mal-dominant major gene model assuming incomplete
sex- and age-dependent penetrance of genotypes [2, 3].
Establishment of the mechanism of the disease
inheritance requires localization and identiﬁcation of
the genes involved in the disease determination .
One of the approaches towards the resolution of this
problem lies in testing of so-called candidate genes for
their implication in the control of the pathology stud-
ied. The candidate genes are chosen based on the bio-
logical nature of the disease. The growth and develop-
ment of the spine involves a lot of metabolic processes.
For this reason, genetic factors affecting metabolism of
the structural components of the spine can be the cause
of the disease. To date, several dozens of mutations
leading to different orthopedic diseases have been
described . Scoliosis is characterized by various
changes in vertebral bodies, intervertebral disks, and in
the neighboring musculature [6, 7]. Primary changes
occur in the vertebral body growth plates , physical
and chemical properties of which depend on their main
components: proteoglycans and ﬁbrillar proteins.
These components form an arrayed structure, which
provides metabolism and nutrition of the proliferating
cartilage tissue .
Several attempts for testing the candidate genes,
responsible for the development of IS were made.
Structural genes encoding elastin, collagen, and ﬁbril-
lin, which form microﬁbrillar component of extracellu-
lar matrix, were examined. None of the genes had
shown linkage with the gene responsible for the devel-
opment of the disease [10–12].
In the present study a gene encoding another com-
ponent of extracellular matrix, proteoglycan, was tested
as a possible candidate gene. Aggrecan is the largest
proteoglycan of the extracellular matrix. The bulk of
the molecule is made of hyaluronic acid and a core pro-
Analysis of Polymorphism of the Number of Tandem Repeats
in the Aggrecan Gene Exon G3 in the Families
with Idiopathic Scoliosis
I. V. Zorkoltseva
, O. A. Lubinsky
, R. N. Sharipov
, A. M. Zaidman
T. I. Axenovich
, and G. M. Dimshits
Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, 630090 Russia;
fax: (3832)33-12-78; e-mail: email@example.com
Novosibirsk Research Institute of Traumatology and Orthopedy, Novosibirsk, 630091 Russia
Received June 21, 2001
—In our previous study we showed that the inheritance of pronounced forms of idiopathic scoliosis
was described by an autosomal-dominant major gene model assuming incomplete sex- and age-dependent pen-
etrance. In the present study a search for the major gene was carried out by means of testing candidate genes.
The aggrecan gene with known polymorphism of the number of tandem repeats in exon G3 was considered to
be one of these candidate genes. Various alleles of this gene provide attachment of different number of chon-
droitin sulfate chains to a proteoglycan core protein, thereby changing functional properties of cartilage. Using
the TDT analysis of 33 unrelated families consisting of a proband and his/her parents, we examined the exist-
ence of associations between the aggrecan alleles and the disease. Among nine alleles identiﬁed, three alleles
with tandem repeats numbers of 25, 26, and 27 prevailed. We did not reveal preferable transmission of any of
these alleles to the proband (TDT-statistics for different alleles varied from 0 to 0.71). There was also no cor-
relation between the number of tandem repeats and the disease severity. Thus, either the polymorphism of the
number of tandem repeats is not the direct reason for development of idiopathic scoliosis in the families tested,
or its effect is too low to be detected using the samples examined.