Analysis of polymorphism of the number of tandem repeats in the aggrecan gene exon G3 in the families with idiopathic scoliosis

Abstract

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 penetrance. 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 chondroitin 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 parents, we examined the existence 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 correlation 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.