Abstract
BackgroundAlthough adolescent idiopathic scoliosis affects approximately 3% of adolescents, the genetic contributions have proven difficult to identify. Work in model organisms, including zebrafish, chickens, and mice, has implicated the lysyl oxidase family of enzymes in the development of scoliosis. We hypothesized that common polymorphisms in the five human lysyl oxidase genes (LOX, LOXL1, LOXL2, LOXL3, and LOXL4) may be associated with the phenotype of adolescent idiopathic scoliosis.MethodsThis was a case-control genetic association study. A total of 112 coding and tag SNPs in LOX, LOXL1, LOXL2, LOXL3, and LOXL4 were genotyped in a discovery cohort of 138 cases and 411 controls. Genotypes were tested for association with adolescent idiopathic scoliosis by logistic regression with a two degree of freedom genotypic model and gender as a covariate. Fourteen SNPs with p < 0.1 in the discovery phase were genotyped in an independent replication cohort of 400 cases and 506 controls.ResultsNo evidence for significant association was found between coding or tag SNPs in LOX, LOXL1, LOXL2, LOXL3, and LOXL4 and the phenotype of adolescent idiopathic scoliosis.ConclusionsDespite suggestive evidence in model organisms, common variants and known coding SNPs in the five human lysyl oxidase genes do not confer increased genotypic risk for adolescent idiopathic scoliosis. The above methodology does not address rare variants or individually private mutations in these genes, and future research may focus on this area.
Highlights
Adolescent idiopathic scoliosis affects approximately 3% of adolescents, the genetic contributions have proven difficult to identify
For initial SNP selection, the Tagger algorithm initially identified a total of 132 candidate coding and tag SNPs
Discussion work in model organisms suggests a role for lysyl oxidases in scoliosis, common variants in the five human lysyl oxidase genes did not show significant association with the adolescent idiopathic phenotype
Summary
Adolescent idiopathic scoliosis affects approximately 3% of adolescents, the genetic contributions have proven difficult to identify. We hypothesized that common polymorphisms in the five human lysyl oxidase genes (LOX, LOXL1, LOXL2, LOXL3, and LOXL4) may be associated with the phenotype of adolescent idiopathic scoliosis. Adolescent idiopathic scoliosis (AIS) affects 2-3% of the pediatric population [1] and often requires bracing or surgical treatment. AIS is currently recognized as a multifactorial disease with multiple influences, both environmental and genetic [2,3]. Multiple attempts have been made to identify the genetic etiologies of AIS with only limited success, despite evidence for genetic contributions. Multiple studies have made a strong case for heritability of the incidence of AIS.
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