title: Association study of BMP4, IL6, Leptin, MMP3, and MTNR1B gene promoter polymorphisms and adolescent idiopathic scoliosis.
abstract: METHODS
  a genetic association study was performed on 126 patients with adolescent idiopathic scoliosis and 197 healthy controls from independent Hungarian pedigrees.
  
  
  OBJECTIVE
  to reveal implication of promoter polymorphisms of bone morphogenetic protein 4 (BMP4), interleukin-6 (IL6), leptin, matrix metalloproteinase-3 (MMP3), melatonin 1B receptor (MTNR1B) genes in adolescent idiopathic scoliosis (AIS). Combinatorial association of these candidate genes was also studied to detect additive effect of certain single-nucleotide polymorphism (SNP) patterns.
  
  
  BACKGROUND
  it was previously unraveled that IL6, MMP3, and MTNR1B genes could be considered as predisposition genes of AIS. Since BMP4 and leptin play a central role in bone formation and remodeling and are in direct interaction with melatonin, IL6, and MMP3, these also can be potential predisposition genes.
  
  
  METHODS
  the genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism.
  
  
  RESULTS
  at a single gene level, no significant differences were found for allele and genotype frequencies of the polymorphisms of these genes between cases or controls; therefore, the formerly detected association of IL6, MMP3, and MTNR1B with AIS was not confirmed in the Hungarian population by independent SNP analysis. However, significantly increased AIS risk was observed at particular combinations of genotypes of paired SNPs of the candidate genes.
  
  
  CONCLUSIONS
  the genetic effect of promoter polymorphisms of BMP4, IL6, leptin, MMP3, and MTNR1B can be synergistic for susceptibility to AIS. The combinatorial effect can modulate the final biological impact of many susceptibility polymorphisms; therefore, this should be considered at the comparison of results from case-control studies of different populations.
authors.affiliation: Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvári Körút 62, H-6726, Szeged, Hungary. morocz@brc.hu
authors.forename: Mónika
authors.initials: M
authors.lastname: Mórocz
authors.forename: Agnes
authors.initials: A
authors.lastname: Czibula
authors.forename: Zsuzsanna B
authors.initials: ZB
authors.lastname: Grózer
authors.forename: Anita
authors.initials: A
authors.lastname: Szécsényi
authors.forename: Péter Z
authors.initials: PZ
authors.lastname: Almos
authors.forename: István
authors.initials: I
authors.lastname: Raskó
authors.forename: Tamás
authors.initials: T
authors.lastname: Illés
mesh_terms: D000293:Adolescent; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D020738:Leptin / Q000235:genetics*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D044123:Receptor, Melatonin, MT2 / Q000235:genetics*; D012600:Scoliosis / Q000235:genetics*; D055815:Young Adult
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D015850:Interleukin-6; D020738:Leptin; D044123:Receptor, Melatonin, MT2; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3