title: Possible control of paternal imprinting of polymorphisms of the ADAM33 gene by epigenetic mechanisms and association with level of airway hyperresponsiveness in asthmatic children.
abstract: BACKGROUND
  ADAM33 is the candidate gene most commonly associated with asthma and airway hyperreactivity (AHR).
  
  
  OBJECTIVE
  The aim of this study was to determine whether level of AHR is associated with certain alleles or haplotypes of the ADAM33 gene in asthmatic children.
  
  
  METHODS
  One hundred and nine asthmatic children and 46 controls from the general population were examined with spirometry before and after histamine and methacholine inhalation. All subjects were genotyped for single-nucleotide polymorphisms (SNPs) of the ADAM33 gene. Haplotypes were determined according to genotypes of the patient's parents.
  
  
  RESULTS
  We found the three most frequent ADAM33 haplotypes (a1-3) were associated with the highest level of AHR to methacholine and histamine in 66% of asthmatic children. The paternally transmitted GGGCTTTCGCA haplotype was seen in 73.3% asthmatic children with serious AHR to methacholine challenge (paternal and maternal origin of haplotype 73.3% to 37.5, P=0.046) Significant differences in the relative frequency of paternal haplotypes with high levels of AHR to histamine were found (P=0.013).
  
  
  CONCLUSIONS
  ADAM33 haplotypes (a1, a2, a3) are associated with severity of AHR and are significantly more often transmitted in the paternal line.
authors: Department of Paediatrics, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic.
authors: Frantisek
authors: F
authors: Kopriva
authors: Marek
authors: M
authors: Godava
authors: Marie
authors: M
authors: Markova
authors: Radek
authors: R
authors: Vodicka
authors: Ladislav
authors: L
authors: Dusek
authors: Jiri
authors: J
authors: Muzik
authors: Eva
authors: E
authors: Schneiderova
authors: Radek
authors: R
authors: Vrtel
authors: Vladimir
authors: V
authors: Mihal
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D001249:Asthma / Q000235:genetics*; D016535:Bronchial Hyperreactivity / Q000235:genetics*; D002648:Child; D044127:Epigenesis, Genetic; D005220:Fathers; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D051722:ADAM Proteins; C450441:ADAM33 protein, human