Lack of association between the aggrecan gene and familial idiopathic scoliosis

A study was conducted to determine the potential association between a specific aggrecan gene polymorphism and familial idiopathic scoliosis (FIS). To determine the allelic distribution of the exon 12 polymorphism within a sample of families with FIS. FIS is a structural curvature of the spine where the underlying genetic etiology has not been established. The aggrecan locus has been linked to multiple skeletal disorders. A polymorphism, within the aggrecan gene, was previously reported to be associated with curve severity in individuals with scoliosis. Fifty-eight families with FIS were genotyped for the aggrecan exon 12 polymorphism using a polymerase chain reaction method. Model-independent sib-pair linkage analyses and tests of association were performed to analyze the genetic effects of the exon 12 polymorphism. Linkage analyses of a genomic screen performed on a subgroup of 48 families with a most likely to be X-linked dominant mode of inheritance of FIS showed marginally significant results on chromosome 15q25-26 (P < 0.05). The overall distribution of the alleles was consistent with previously reported literature; no evidence of association and marginal significance of linkage was found between the polymorphism and FIS or the degree of lateral curvature. Despite the negative association reported here, further investigation of the gene and its potential association to FIS is required.