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Idiopathic scoliosis has been studied through centuries, but problems of its aetiology and pathogenesis up till now are the subjects of considerable discussion. Pathogenetic mechanism of the spine deformity development in idiopathic scoliosis (IS) was established on the basis of in-depth morphological and biochemical investigations of structural components of the spine in patients with IS (surgical material) (Zaidman A.M., et al. 2001). It was shown that IS develops on the basis of disturbance of proteoglycans (PG) synthesis and formation in vertebral growth plates. Decrease of chondroitin sulphate component of PG and increase of keratan sulphate one, as well as decrease in degree of sulphating of glycosaminoglycan (GAG) chains and increase of non-acetilated sugars – all this evidences for conformational changes in proteoglycans. The found keratan sulphate-related fraction is likely a marker of genetic changes in PGs in idiopathic scoliosis. Structural changes in PGs in combination with reduce of quantity of diffuse molecules which perform trophic and informational function, and disorders of receptor function of chondroblast membranes (ultra structural and histochemical findings) are the factors of disorders in regulation mechanisms of vertebral growth plate cells and matrix differentiation and reproduction.

Long-term studies (Zaidman A.M., et al., 1999–2003) demonstrated a major-gene effect in Idiopathic Scoliosis. The next stage was major gene localization by the method for candidate gene testing. 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 chondroitin sulfate chains to a proteoglycan core protein, thereby changing functional properties of cartilage. The aggrecan gene AGC1 coding a core protein of aggrecan molecule has been localised to region 15q2b. In anald families nine alleles of aggrecan gene have been identified, among them 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 The absence of reliable association of IS with polymorphism of exon G3 can not be interpreted as a non-linkage of the whole aggrecan gene to IS development determination.

As the linkage of other proteoglycans to IS development has not been excluded, we perform the RT-PCR and immunoblot analyses of the expression of main PG genes and their protein products in cultivated chondroblasts isolated from vertebral growth plates in 15 patients with III–IV grade IS (surgical material). The study has shown that aggrecan gene expression is significantly decreased in cultivated chondroblasts from patients with IS, what correlates with a decrease of synthesed protein product, both in cells (chondrocytes) isolated from IS patients and in cultural media. The presence of keratan sulphate-related fraction and keratan sulphate increase are associated with luminicene increase. In present we perform a sequencing of aggrecan genome.

Correspondence should be addressed to Jeremy C T Fairbank at The Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford OX7 7LD, UK