title: Genetic variants in melatonin synthesis and signaling pathway are not associated with adolescent idiopathic scoliosis.
abstract: METHODS
  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.
  
  
  BACKGROUND
  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.
authors.affiliation: Axial Biotech, Inc, Salt Lake City, Utah, USA. lnelson@axialbiotech.com
authors.forename: Lesa M
authors.initials: LM
authors.lastname: Nelson
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ward
authors.forename: James W
authors.initials: JW
authors.lastname: Ogilvie
mesh_terms: D000121:Acetylserotonin O-Methyltransferase / Q000235:genetics; D000293:Adolescent; D047068:Arylalkylamine N-Acetyltransferase / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008550:Melatonin / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D051745:Protein Kinase C-delta / Q000235:genetics; D011859:Radiography; D044122:Receptor, Melatonin, MT1 / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D012600:Scoliosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics; D014481:United States
chemical_list: D044122:Receptor, Melatonin, MT1; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase; D000121:Acetylserotonin O-Methyltransferase; D047068:Arylalkylamine N-Acetyltransferase; C497258:PRKCD protein, human; D051745:Protein Kinase C-delta; D008550:Melatonin