Lack of association between the aggrecan gene and familial idiopathic scoliosis.
METHODS
A study was conducted to determine the potential association between a specific aggrecan gene polymorphism and familial idiopathic scoliosis (FIS).


OBJECTIVE
To determine the allelic distribution of the exon 12 polymorphism within a sample of families with FIS.


BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Despite the negative association reported here, further investigation of the gene and its potential association to FIS is required.
Marosy
Beth
B
Johns Hopkins University, Baltimore, MD, USA. bmarosy@jhmi.edu
Justice
Cristina M
CM
Nzegwu
Nneka
N
Kumar
Gunjan
G
Wilson
Alexander F
AF
Miller
Nancy H
NH
D000328:Adult; D053674:Aggrecans; D000483:Alleles; D002648:Child; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D012600:Scoliosis / Q000235:genetics*
D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type