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.
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 AISpatients 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 AISpatients. 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.