MMP-9 gene variants increase the risk for non-atopic asthma in children

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.