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.