Common polymorphisms in human lysyl oxidase genes are not associated with the adolescent idiopathic scoliosis phenotype

This 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.No 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.Despite 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.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. A meta-analysis of 68 sets of twins found concordance in 73% of monozygous twins and 36% of dizygous twins [4]. A more recent study relying on self report survey methodology confirmed the increased concordance in monozygotic twin pairs (6/44) relative to dizygotic pairs (0/91) [5]. The search for underlying genes has only uncovered a few viable candidates, namely SNTG1 [6] and CHD7 [7]. Additionally, a recent genome-wide agnostic approach put forward a promising finding in CHL1, but the authors were unab