title: MMP-9 gene variants increase the risk for non-atopic asthma in children.
abstract: BACKGROUND
  Atopic and non-atopic wheezing may be caused by different etiologies: while eosinophils are more important in atopic asthmatic wheezers, neutrophils are predominantly found in BAL samples of young children with wheezing. Both neutrophils as well as eosinophils may secrete matrix metalloproteinase 9 (MMP-9). Considering that MMP-9 plays an important role in airway wall thickening and airway inflammation, it may influence the development of obstructive airway phenotypes in children. In the present study we investigated whether genetic variations in MMP-9 influence the development of different forms of childhood asthma.
  
  
  METHODS
  Genotyping of four HapMap derived tagging SNPs in the MMP-9 gene was performed using MALDI-TOF MS in three cross sectional study populations of German children (age 9-11; N = 4,264) phenotyped for asthma and atopic diseases according to ISAAC standard procedures. Effects of single SNPs and haplotypes were studied using SAS 9.1.3 and Haploview.
  
  
  RESULTS
  SNP rs2664538 significantly increased the risk for non-atopic wheezing (OR 2.12, 95%CI 1.40-3.21, p < 0.001) and non-atopic asthma (OR 1.66, 95%CI 1.12-2.46, p = 0.011). Furthermore, the minor allele of rs3918241 may be associated with decreased expiratory flow measurements in non-atopic children. No significant effects on the development of atopy or total serum IgE levels were observed.
  
  
  CONCLUSIONS
  Our results have shown that homozygocity for MMP-9 variants increase the risk to develop non-atopic forms of asthma and wheezing, which may be explained by a functional role of MMP-9 in airway remodeling. These results suggest that different wheezing disorders in childhood are affected differently by genetic alterations.
authors.affiliation: Department of Pediatric Pneumology and Neonatology, Hannover Medical School, Hannover, Germany.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Pinto
authors.forename: Martin
authors.initials: M
authors.lastname: Depner
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Christian
authors.initials: C
authors.lastname: Vogelberg
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
mesh_terms: D001249:Asthma / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005858:Germany / Q000453:epidemiology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000453:epidemiology / Q000235:genetics; D015994:Incidence; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
chemical_list: D020780:Matrix Metalloproteinase 9