title: Association of single nucleotide polymorphisms in the diamine oxidase gene with diamine oxidase serum activities.
abstract: BACKGROUND
  Histamine intolerance (HIT) is associated with an excess of histamine because of an impaired function of the histamine-degrading enzyme diamine oxidase (DAO). The genetic background of HIT is unknown yet.
  
  
  METHODS
  Case-control association study of all haplotype tagging and four previously reported DAO SNPs and one HNMT Single nucleotide polymorphism with symptoms of HIT and DAO serum activity in 484 German individuals including 285 patients with clinical symptoms of HIT and 199 controls.
  
  
  RESULTS
  Diamine oxidase serum activity was significantly associated with seven SNPs within the DAO gene. The minor allele at rs2052129, rs2268999, rs10156191 and rs1049742 increased the risk for a reduced DAO activity whereas showing a moderate protective effect at rs2071514, rs1049748 and rs2071517 in the genotypic (P = 2.1 × 10(-8) , 7.6 × 10(-10) , 8.3 × 10(-10) , 0.009, 0.005, 0.00001, 0.006, respectively) and allelic genetic model (P = 2.5 × 10(-11) , 5.4 × 10(-13) , 8.9 × 10(-13) , 0.00002, 0.006, 0.0003, 0.005, respectively). Reporter gene assays at rs2052129 revealed a lower promoter activity (P = 0.016) of the minor allele. DAO mRNA expression in peripheral blood mononuclear cells of homozygous carriers of the minor allele at rs2052129, rs2268999, rs10156191 was lower (P = 0.002) than homozygous carriers of the major allele. Diamine oxidase variants were not associated with the HIT phenotype per se, only with DAO activity alone and the subgroup of HIT patients displaying a reduced DAO activity.
  
  
  CONCLUSIONS
  DAO gene variants strongly influence DAO expression and activity but alone are not sufficient to fully effectuate the potentially associated disease state of HIT, suggesting an interplay of genetic and environmental factors.
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Maintz
authors.forename: C-F
authors.initials: CF
authors.lastname: Yu
authors.forename: E
authors.initials: E
authors.lastname: Rodríguez
authors.forename: H
authors.initials: H
authors.lastname: Baurecht
authors.forename: T
authors.initials: T
authors.lastname: Bieber
authors.forename: T
authors.initials: T
authors.lastname: Illig
authors.forename: S
authors.initials: S
authors.lastname: Weidinger
authors.forename: Natalija
authors.initials: N
authors.lastname: Novak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006631:Amine Oxidase (Copper-Containing) / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005512:Food Hypersensitivity / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D005858:Germany; D006239:Haplotypes; D006632:Histamine / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D006632:Histamine; D006631:Amine Oxidase (Copper-Containing)