STUDY DESIGN: Genetic association study investigating the association of genetic 
markers of melatonin signaling and biosynthesis with adolescent idiopathic 
scoliosis (AIS).
OBJECTIVE: To determine whether gene polymorphisms related to the melatonin 
signaling or biosynthesis pathways are associated with AIS.
SUMMARY OF BACKGROUND DATA: Data have been published on the potential role of 
gene polymorphisms for melatonin receptor (MTNR) 1B in predicting AIS. Other 
genes in the melatonin pathways have been tested for association with AIS.
METHODS: The following genes involved in melatonin synthesis were evaluated 
herein: tryptophan 5-hyroxylase 1 (TPH1), serotonin N-acetyltransferase (SNAT), 
and hydroxyindoleo-methyltransferase (HIOMT). In addition, proteins involved in 
melatonin signaling were also included in this study: MTNR1A, MTNR1B, and 
protein kinase C delta (PKCd). High throughput microarray-based single 
nucleotide polymorphism (SNP) genotyping was performed for these seven genes 
using DNA samples from 589 AIS subjects and 1533 ethnically matched controls. 
Chi-square analyses of allele frequency between AIS cases and controls were 
performed and odds ratios were calculated for all SNP markers.
RESULTS: Three SNPs were tested for both MTNR1A and HIOMT, 4 for TPH1 and SNAT, 
12 for PKCd, and 7 for MTNR1B. The minor allele frequencies were not 
significantly different between AIS cases and controls. No association was thus 
found between AIS and the investigated SNPs.
CONCLUSIONS: Genetic polymorphisms associated with either melatonin synthesis or 
its signaling pathway are unlikely to be commonly associated with AIS.