STUDY DESIGN: A genetic association study of tryptophan hydroxylase 1 gene 
(TPH1) and arylalkylamine N-acetyltransferase gene(AANAT) with adolescent 
idiopathic scoliosis (AIS) in Han Chinese.
OBJECTIVE: To access whether TPH1 and AANAT polymorphisms are associated with 
the predisposition, gender, and/or severity of AIS.
SUMMARY OF BACKGROUND DATA: Studies have shown that AIS is a multifactorial 
inheritance disease, but the etiology is still unknown. In addition, several 
lines of evidence show that melatonin deficiency is closely associated with AIS, 
although there are still doubts and debates. Some polymorphisms in TPH1 and 
AANAT, the genes of 2 critical enzymes involved in melatonin biosynthesis, may 
contribute to variability of melatonin production in pineal glands.
METHODS: We genotyped 16 reported single nuclear polymorphisms (SNPs) present in 
TPH1 and AANAT in 103 AIS patients and 108 controls with matched sex and age. 
The data of 6 SNPs with minor allele frequence (MAF) above 5% were analyzed by 
the allelic and genotypic association analysis, the genotype-phenotype (gender 
and Cobb angle) association analysis, and the haplotype analysis.
RESULTS: The single SNP analysis showed that rs10488682, located in the promoter 
region of TPH1, was related with the occurrence of AIS (P < 0.05). No SNP was 
found to be correlated with gender or Cobb angle. Two makers (rs8176799 and 
rs2108977) in TPH1 were found to be in strong LD [ D' = 1.0 (95% CI, 0.9-1.0), 
gamma = 0.501, LOD = 18.93] in the controls. Both global haplotype analysis and 
individual haplotype analysis showed that there was no haplotype significantly 
associated with AIS in this LD block.
CONCLUSION: TPH1 polymorphisms were associated with AIS but not with gender and 
Cobb angle in AIS patients. AANAT polymorphisms were not associated with AIS. 
These results suggested that TPH1 was an AIS predisposition gene, and there was 
a close relationship between the dyssynthesis of melatonin and AIS.