Adolescent idiopathic scoliosis (AIS), environment, exposome and epigenetics: a molecular perspective of postnatal normal spinal growth and the etiopathogenesis of AIS with consideration of a network approach and possible implications for medical therapy

The principal aim of this paper is to examine the etiopathogenesis of adolescent idiopathic scoliosis (AIS) from the standpoint of epigenetics. To our knowledge this has not previously been addressed. Epigenetics, a relatively recent field now vast and vigorous, evaluates factors concerned with gene expression in relation to environment, disease, normal development and aging, with a complex regulation across the genome during the first decade of life. Butcher and Beck [1] describe epigenetics as follows:"Although environmental measures are logical covariants for genotype-phenotype investigations, another non-genetic intermediary exists: epigenetics. Epigenetics is the analysis of somatically-acquired and, in some cases, transgenerationally inherited epigenetic modifications that regulate gene expression, and offers to bridge the gap between genetics and environment to understand phenotype. The most widely studied epigenetic mark is DNA methylation. Aberrant methylation at gene promoters is strongly implicated in disease etiology, most notably cancer."There is controversy relating to the definition of epigenetics which we outline. Taking the broad definition, a view of AIS etiopathogenesis and normal spinal development is presented from an epigenetic standpoint, predicated on a model for other diseases.Research into the causation of adolescent idiopathic scoliosis (AIS) draws heavily from mechanical and biological disciplines, but still lacks an agreed theory of etiopathogenesis [2,3]. Genetic factors are believed to play an important role in the etiology of AIS with considerable heterogeneity [2,4,5]. Hence treatment is empirical and not based on sufficient understanding of etiology to support the current mechanically-based therapy [6]. The research problem is complicated by the suspicion that AIS may result not from one cause, but several that interact. Genetic, and now genomic, research on AIS has not yet provided the therapeutically-required etiologic understandi