Abstract
Introduction: Lower Respiratory Tract Infection (LRTI) is one of the leading reasons for seeking medical care in Europe. However, not everyone is equally susceptible to LRTI.
Aims and objectives: To identify host genetic factors that may play an important role in explaining this inter-individual variation in susceptibility to LRTI.
Methods: DNA was extracted from blood samples of 3000 cases and 3000 matched controls recruited within the GRACE study. Single nucleotide polymorphisms (SNPs) in 19 genes, selected based on our earlier studies on severe LRTI (invasive pneumococcal disease (IPD)), were genotyped with Sequenom's iPLEX technology.
Results: SNPs in the genes PTPN22 (Arg620Trp: p=0.037, OR 2.0) and NFKBIZ (rs616597: p=0.022, OR 0.87; rs600718: p=0.028, OR 0.87) associated with LRTI in the initial analysis which included half of the cases and controls. PTPN22 is a lymphoid specific protein tyrosine phosphatase that regulates the immune response through T-cell signalling. NFKBIZ is one of the NFκB inhibitors and thereby affects the transcription of pro-inflammatory genes. Genotyping of the rest of the samples is ongoing. In addition, more candidate genes possibly involved in the host immune response to viral infections will be genotyped. In the further analyses, cases will be subdivided based on the microbiological cause of their LRTI, namely between bacterial and viral infection, and further to specific pathogens.
Conclusions: Host genetic factors involved in the pathogenesis of IPD might also be important in defence against milder LRTIs. Identification of these factors may potentially lead to more individualised detection, treatment, and prevention of LRTIs.
- © 2011 ERS
