Background: Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity in children. Studies have shown low melatonin levels resulting from pinealectomy in chickens and mice result in the development scoliosis, whereas supplementation with melatonin after the pinealectomy prevented it. The mere characterization of low melatonin levels is not sufficient to explain the development of idiopathic scoliosis in primates and humans, but we hypothesize that a mutation in melatonin-related receptors may be involved with the development of scoliosis.
Methods: The coding, splice-site, and promoter regions of 3 melatonin-related receptors (hMel-1B, RORalpha, and GPR50) were evaluated by DNA sequencing for variants associated with the phenotype of adolescent idiopathic scoliosis. An initial screening of 50 scoliosis patients with adolescent idiopathic scoliosis was compared with 50 controls by DNA sequencing of the 3 receptors. Additional cases and controls were evaluated when genetic variants were observed (for a total of 885 individuals).
Results: No significant differences were found in the hMel-1B and RORalpha receptors. We found 2 cSNPs in GPR50 (rs561077 and rs13440581) in the initial 50 patients. To evaluate the significance of these cSNPs, an additional 356 patients and 429 controls were analyzed. When the combined groups were analyzed, no significant associations were observed.
Conclusions: Despite the observed relationship between melatonin and scoliosis, there is no significant association between mutations found in any known melatonin-related receptors with adolescent idiopathic scoliosis. The strong evidence of a melatonin-related cause for the development of idiopathic scoliosis still encourages research into undiscovered melatonin-related receptors, melatonin-related hormones, and the catalytic enzymes for the serotonin-melatonin pathway.
Clinical relevance: This investigation is a genetic testing of the remaining currently known melatonin-related receptors that have not been analyzed earlier for association with AIS. Given the support in the literature of a relationship between melatonin and AIS, we have shown no mutations in any of the known melatonin-related receptor in patients with AIS.