STUDY DESIGN: A genetic association study to comprehensively investigate 
variations of melatonin receptor 1B gene polymorphism by a set of tagging single 
nucleotide polymorphisms (tagSNPs) derived from the International Hapmap 
project.
OBJECTIVES: To determine whether melatonin receptor 1B (MTNR1B) gene 
polymorphisms are associated with the predisposition and/or disease severity of 
adolescent idiopathic scoliosis (AIS).
SUMMARY OF BACKGROUND DATA: Linkage studies suggested a genetic predisposition 
for AIS. In addition, evidence showed that AIS might be related to melatonin 
deficiency and dysfunction of melatonin signaling pathway. Locating in one of 
the chromosomal regions linked to AIS, MTNR1B gene is a potential candidate gene 
for AIS.
METHODS: This study was carried out in 2-stage case-control analysis: 1) initial 
screening (472 cases and 304 controls) and 2) separate replication test (342 
cases and 347 controls) to confirm results in the screening. In the first 
screening stage, 5 tagSNPs were selected to cover most of the genetic variation 
in the MTNR1B gene. In the second stage, SNPs showing association in the 
screening stage were studied in a separate replication sample set to confirm the 
association. Genotyping was performed by PCR-RFLP.
RESULTS: The first stage showed a putative association between rs4753426 and 
AIS, which was confirmed in the replication sample set. By meta-analysis, the 
frequency of C allele of this SNP locating in the promoter was significantly 
higher in the cases than controls (P = 0.006 aftermeta-analysis). Subjects with 
the CC genotype had an odds ratio of 1.29 for AIS. Another SNP rs741837 in 
promoter region, being moderate linkage disequilibrium with rs4753426, was also 
marginally associated with AIS.
CONCLUSION: Polymorphisms of the promoter of MTNR1B gene were associated with 
AIS, but not with the curve severity in AIS patients. This suggested that MTNR1B 
was an AIS predisposition gene.