Impact of IL8 and IL8-receptor alpha polymorphisms on the genetics of bronchial asthma and severe RSV infections.
BACKGROUND
Interleukin 8 (IL8) belongs to the family of chemokines. It mediates the activation and migration of neutrophils from peripheral blood into tissue and hereby plays a pivotal role in the initiation of inflammation. Thus it is important in inflammatory lung diseases like bronchial asthma or severe infections by Respiratory Syncytial Virus (RSV). IL8 acts through binding to the IL8-Receptor alpha (IL8RA). For both genes association with asthma has been described. In addition, IL8 has been found in association with RSV bronchiolitis. The aim of our study was to test both genes for association with asthma and severe RSV infections. In addition we were interested in whether a common genetic background of both diseases exists in regards to these genes.


METHODS
We genotyped the two IL8 promotor polymorphisms -251A/T and -781C/T and the three amino acid variants M31R, S276T and R335C in IL8RA on 322 children with asthma, 131 infants with severe RSV associated diseases and 270 controls. Statistical analyses made use of the Armitage's trend test for single polymorphisms and FAMHAP for calculations of haplotypes.


RESULTS
We found association of the IL8 polymorphism -781C/T as well as IL8 haplotypes with asthma (p = 0.011 and p = 0.036, respectively). In addition, direct comparison of the asthmatic population with the RSV population revealed significant differences, both for -781C/T alone (p = 0.034) and IL8 haplotypes (p = 0.005). The amino acid variants in IL8RA were evenly distributed in between all three populations.


CONCLUSIONS
We conclude from our data that IL8 might play a role in the genetic predisposition to asthma and that these effects are different or even opposite to the effects on severe RSV diseases. Furthermore, IL8RA is unlikely to play a major role in the genetics of either disease.
Puthothu
Beena
B
University Children's Hospital, University of Freiburg, Mathildenstrasse 1, D-79106 Freiburg, Germany. beenamary@hotmail.com
Krueger
Marcus
M
Heinze
Jessica
J
Forster
Johannes
J
Heinzmann
Andrea
A